Atherosclerosis - Knowledge

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sub-endothelium, the repair has to end up with altered remodeling of local endothelium. This is the manifestation of a misrepair. Important is this altered remodeling makes the local endothelium have increased fragility to damage and have reduced repair efficiency. As a consequence, this part of endothelium has an increased risk factor of being injured and improperly repaired. Thus, the accumulation of misrepairs of endothelium is focalized and self-accelerating. In this way, the growing of a plaque is also self-accelerating. Within a part of the arterial wall, the oldest plaque is always the biggest, and is the most dangerous one to cause blockage of a local artery.

65: 1353: 1167: 1364: 499: 1431: 862: 1395:, in general. However, these methods focus on detecting only severe narrowing, not the underlying atherosclerosis disease. As demonstrated by human clinical studies, most severe events occur in locations with heavy plaque, yet little or no lumen narrowing present before debilitating events suddenly occur. Plaque rupture can lead to artery lumen occlusion within seconds to minutes, and potential permanent debility, and sometimes sudden death. 7961: 1486:. Both anatomic and physiologic methods allow early detection before symptoms show up, disease staging, and tracking of disease progression. Anatomic methods are more expensive and some of them are invasive in nature, such as IVUS. On the other hand, physiologic methods are often less expensive and safer. But they do not quantify the current state of the disease or directly track progression. In recent years, developments in 1119:, and cellular debris. In advanced plaques, the central core of the plaque usually contains extracellular cholesterol deposits (released from dead cells), which form areas of cholesterol crystals with empty, needle-like clefts. At the periphery of the plaque are younger "foamy" cells and capillaries. These plaques usually produce the most damage to the individual when they rupture. Cholesterol crystals may also play a role. 801:. It is characterized by a remodeling of arteries leading to subendothelial accumulation of fatty substances called plaques. The buildup of an atheromatous plaque is a slow process, developed over a period of several years through a complex series of cellular events occurring within the arterial wall and in response to a variety of local vascular circulating factors. One recent hypothesis suggests that, for unknown reasons, 356:. Though it was first described in 1575, there is evidence suggesting that this disease state is genetically inherent in the broader human population, with its origins tracing back to genetic mutations that may have occurred more than two million years ago during the evolution of hominin ancestors of modern human beings. 1016:

atheromatous plaque interfering with the regulation of the calcium deposition, it accumulates and crystallizes. A similar form of intramural calcification, presenting the picture of an early phase of arteriosclerosis, appears to be induced by many drugs that have an antiproliferative mechanism of action (

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and osteochondrocytes. Importantly, genetic lineage-tracing experiments have unequivocally shown that 40-90% of plaque-resident cells are vascular smooth muscle cell derived, therefore, it is important to research the role of vascular smooth muscle cells in atherosclerosis to identify new therapeutic

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rich oils such as fish oil, when being sold in pill form, can hide the taste of oxidized or rancid fat that might be present. In the US, the health food industry's dietary supplements are self-regulated and outside of FDA regulations. To properly protect unsaturated fats from oxidation, it is best to

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prior to excretion. Therefore, we know that ABCA1 plays an important role in preventing cholesterol accumulation in macrophages. By enhancing miR-33 function, the level of ABCA1 is decreased, leading to decrease cellular cholesterol efflux to apoA-1. On the other hand, by inhibiting miR-33 function,

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Medical treatments often focus on alleviating symptoms. However measures which focus on decreasing underlying atherosclerosis—as opposed to simply treating symptoms—are more effective. Non-pharmaceutical means are usually the first method of treatment, such as stopping smoking and practicing regular

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Repeated plaque ruptures, ones not resulting in total lumen closure, combined with the clot patch over the rupture and healing response to stabilize the clot is the process that produces most stenoses over time. The stenotic areas tend to become more stable despite increased flow velocities at these

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of the blood vessel to stretch, compensating for the additional bulk. The endothelial lining then thickens, increasing the separation between the plaque and lumen. The thickening somewhat offsets the narrowing caused by the growth of the plaque, but moreover, it causes the wall to stiffen and become

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or closure of the lumen, or over time and after repeated ruptures, resulting in a persistent, usually localized stenosis or blockage of the artery lumen. Stenoses can be slowly progressive, whereas plaque ulceration is a sudden event that occurs specifically in atheromas with thinner/weaker fibrous

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are only detectable at that particular severity of stenosis. However, clinical trials have shown that only about 14% of clinically debilitating events occur at sites with more than 75% stenosis. The majority of cardiovascular events that involve sudden rupture of the atheroma plaque do not display

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supply blood to the brain and neck. Marked narrowing of the carotid arteries can present with symptoms such as: a feeling of weakness; being unable to think straight; difficulty speaking; dizziness; difficulty in walking or standing up straight; blurred vision; numbness of the face, arms and legs;

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Zimmer S, Grebe A, Bakke SS, Bode N, Halvorsen B, Ulas T, Skjelland M, De Nardo D, Labzin LI, Kerksiek A, Hempel C, Heneka MT, Hawxhurst V, Fitzgerald ML, Trebicka J, Björkhem I, Gustafsson JÅ, Westerterp M, Tall AR, Wright SD, Espevik T, Schultze JL, Nickenig G, Lütjohann D, Latz E (April 2016).

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The key to the more effective approaches is to combine multiple different treatment strategies. In addition, for those approaches, such as lipoprotein transport behaviors, which have been shown to produce the most success, adopting more aggressive combination treatment strategies taken on a daily

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medications are routinely used to control blood pressure. If the combined efforts of risk factor modification and medication therapy are not sufficient to control symptoms or fight imminent threats of ischemic events, a physician may resort to interventional or surgical procedures to correct the

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From clinical trials, 20% is the average stenosis at plaques that subsequently rupture with resulting complete artery closure. Most severe clinical events do not occur at plaques that produce high-grade stenosis. From clinical trials, only 14% of heart attacks occur from artery closure at plaques

1158:(some argue for 90 units) has been the radiographic density usually accepted as clearly representing tissue calcification within arteries. These deposits demonstrate unequivocal evidence of the disease, relatively advanced, even though the lumen of the artery is often still normal by angiography. 1142:

However, atheromas within the vessel wall are soft and fragile with little elasticity. Arteries constantly expand and contract with each heartbeat, i.e., the pulse. In addition, the calcification deposits between the outer portion of the atheroma and the muscular wall, as they progress, lead to a

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work by inhibiting HMG-CoA (hydroxymethylglutaryl-coenzyme A) reductase, a hepatic rate-limiting enzyme in cholesterol's biochemical production pathway. By inhibiting this rate-limiting enzyme, the body is unable to produce cholesterol endogenously, therefore reducing serum LDL-cholesterol. This

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with few side effects. Secondary prevention therapy, which includes high-intensity statins and aspirin, is recommended by multi-society guidelines for all patients with history of ASCVD (atherosclerotic cardiovascular disease) to prevent recurrence of coronary artery disease, ischemic stroke, or

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A controlled exercise program combats atherosclerosis by improving circulation and functionality of the vessels. Exercise is also used to manage weight in patients who are obese, lower blood pressure, and decrease cholesterol. Often lifestyle modification is combined with medication therapy. For

1295:. Atherosclerotic lesions, or atherosclerotic plaques, are separated into two broad categories: Stable and unstable (also called vulnerable). The pathobiology of atherosclerotic lesions is very complicated, but generally, stable atherosclerotic plaques, which tend to be asymptomatic, are rich in 1098:

of the arteries, typically without narrowing the lumen due to compensatory expansion of the bounding muscular layer of the artery wall. Beneath the endothelium, there is a "fibrous cap" covering the atheromatous "core" of the plaque. The core consists of lipid-laden cells (macrophages and smooth

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cells of the surrounding muscular layer, specifically in the muscle cells adjacent to atheromas and on the surface of atheroma plaques and tissue. In time, as cells die, this leads to extracellular calcium deposits between the muscular wall and outer portion of the atheromatous plaques. With the

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components. However, in addition to the fibrous cap, vascular smooth muscle cells also give rise to many of the cell types found within the plaque core and can modulate their phenotype to both promote and reduce plaque stability. Vascular smooth muscle cells exhibit pronounced plasticity within

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in the brain and that of age spots on the skin. Misrepair-accumulation aging theory suggests that misrepair mechanisms play an important role in the focal development of atherosclerosis. Development of a plaque is a result of repair of injured endothelium. Because of the infusion of lipids into

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The fibrous plaque is also localized under the intima, within the wall of the artery resulting in thickening and expansion of the wall and, sometimes, spotty localized narrowing of the lumen with some atrophy of the muscular layer. The fibrous plaque contains collagen fibers

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severe headache; and loss of consciousness. These symptoms are also related to stroke (death of brain cells). Stroke is caused by marked narrowing or closure of arteries going to the brain; lack of adequate blood supply leads to the death of the cells of the affected tissue.

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in early 2006. Ongoing work starting in the 1990s may lead to human clinical trials—probably by about 2008. These may use synthesized Apo-A1 Milano HDL directly, or they may use gene-transfer methods to pass the ability to synthesize the Apo-A1 Milano HDLipoprotein.

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reduced endogenous cholesterol production triggers the body to then pull cholesterol from other cellular sources, enhancing serum HDL-cholesterol. These data are primarily in middle-age men and the conclusions are less clear for women and people over the age of 70.

446:, which supply blood to the legs, arms and pelvis, also experience marked narrowing due to plaque rupture and clots. Symptoms of the narrowing are numbness within the arms or legs, as well as pain. Another significant location for plaque formation is the 4614:

Robbins CS, Hilgendorf I, Weber GF, Theurl I, Iwamoto Y, Figueiredo JL, Gorbatov R, Sukhova GK, Gerhardt LM, Smyth D, Zavitz CC, Shikatani EA, Parsons M, van Rooijen N, Lin HY, Husain M, Libby P, Nahrendorf M, Weissleder R, Swirski FK (September 2013).

1721:. Despite the average age of the soldiers being just 22 years old, 77% of them had visible signs of coronary atherosclerosis. This study showed that heart disease could affect people at a younger age and was not just a problem for older individuals. 1969:

mediates transport of cholesterol from peripheral tissues to Apolipoprotein-1 and it is also important in the reverse cholesterol transport pathway, where cholesterol is delivered from peripheral tissue to the liver, where it can be excreted into

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Methods to increase HDL particle concentrations, which in some animal studies largely reverses and removes atheromas, are being developed and researched. However, increasing HDL by any means is not necessarily helpful. For example, the drug

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is the most important risk factor for cardiovascular problems. The causative basis by which aging mediates its impact, independently of other recognized risk factors, remains to be determined. Evidence has been reviewed for a key role of

376:, occurs. Signs and symptoms only occur after severe narrowing or closure impedes blood flow to different organs enough to induce symptoms. Most of the time, patients realize that they have the disease only when they experience other 1319:

formation in the lumen. Upon formation, intraluminal thrombi can occlude arteries outright (e.g., coronary occlusion), but more often they detach, move into the circulation, and eventually occlude smaller downstream branches causing

6664:"Atherosclerosis in children and young adults: An overview of the World Health Organization and International Society and Federation of Cardiology study on Pathobiological Determinants of Atherosclerosis in Youth study (1985–1995)" 1057:

These capped fatty deposits (now called 'atheromas') produce enzymes that cause the artery to enlarge over time. As long as the artery enlarges sufficiently to compensate for the extra thickness of the atheroma, then no narrowing

5842:"2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines" 1458:

and stress-testing, other detection techniques have been developed in the past decades for earlier detection of atherosclerotic disease. Some of the detection approaches include anatomical detection and physiologic measurement.

5134:"A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association" 1845:

HDL in people with unstable angina produced a fairly dramatic reduction in measured coronary plaque volume in only six weeks vs. the usual increase in plaque volume in those randomized to placebo. The trial was published in

2082:(TMAO). Its levels have been associated with atherosclerosis in human studies and animal research suggest that there can be a causal relation. An association between the bacterial genes encoding trimethylamine lyases — the 1027:(LDL) particles. To attract and stimulate macrophages, the cholesterol must be released from the LDL particles and oxidized, a key step in the ongoing inflammatory process. The process is worsened if it is insufficient 1410:

formation. The thrombus then travels downstream to other blood vessels, where the blood clot may partially or completely block blood flow. If the blood flow is completely blocked, cell deaths occur due to the lack of

231:. This is a chronic inflammatory disease involving many different cell types, and driven by elevated levels of cholesterol in the blood. These lesions may lead to narrowing of the arterial walls due to buildup of 8044: 8021: 5257:

McNeal CJ, Dajani T, Wilson D, Cassidy-Bushrow AE, Dickerson JB, Ory M (January 2010). "Hypercholesterolemia in youth: opportunities and obstacles to prevent premature atherosclerotic cardiovascular disease".

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Rancid fats and oils taste very unpleasant in even small amounts, so people avoid eating them. It is very difficult to measure or estimate the actual human consumption of these substances. Highly unsaturated

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exercise. If these methods do not work, medicines are usually the next step in treating cardiovascular diseases and, with improvements, have increasingly become the most effective method over the long term.

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Nordmann AJ, Suter-Zimmermann K, Bucher HC, Shai I, Tuttle KR, Estruch R, Briel M (September 2011). "Meta-analysis comparing Mediterranean to low-fat diets for modification of cardiovascular risk factors".

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Yap SC, Choo YM, Hew NF, Yap SF, Khor HT, Ong AS, Goh SH (December 1995). "Oxidative susceptibility of low density lipoprotein from rabbits fed atherogenic diets containing coconut, palm, or soybean oils".

1062:") of the opening ("lumen") occurs. The artery becomes expanded with an egg-shaped cross-section, still with a circular opening. If the enlargement is beyond proportion to the atheroma thickness, then an 4048:

This early analysis from MESA suggests that higher long-term PM2.5 concentrations are associated with increased IMT progression and that greater reductions in PM2.5 are related to slower IMT progression.

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The distribution of atherosclerotic plaques in a part of arterial endothelium is inhomogeneous. The multiple and focal development of atherosclerotic changes is similar to that in the development of

480:. A much-cited report involved the autopsies of 300 U.S. soldiers killed in Korea. Although the average age of the men was 22.1 years, 77.3 percent had "gross evidence of coronary arteriosclerosis". 2465:"Cyclic phosphatidic acid inhibits the secretion of vascular endothelial growth factor from diabetic human coronary artery endothelial cells through peroxisome proliferator-activated receptor gamma" 1861:

is the most effective agent currently known for raising HDL (by up to 60%). However, in clinical trials, it also raised deaths by 60%. All studies regarding this drug were halted in December 2006.

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If the fibrous cap separating a soft atheroma from the bloodstream within the artery ruptures, tissue fragments are exposed and released. These tissue fragments are very clot-promoting, containing

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Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, Lopez-Sendon J, Mosca L, Tardif JC, Waters DD, Shear CL, Revkin JH, Buhr KA, Fisher MR, Tall AR, Brewer B (November 2007).

3486:"Benefits & risks of statin therapy for primary prevention of cardiovascular disease in Asian Indians - a population with the highest risk of premature coronary artery disease & diabetes" 1498:

Up to 90% of cardiovascular disease may be preventable if established risk factors are avoided. Medical management of atherosclerosis first involves modification to risk factors–for example, via

1895:, that are a model for human-like lipoprotein metabolism, adding D-PUFAs to diet indeed reduced body weight gain, improved cholesterol handling and reduced atherosclerotic damage to the aorta. 1816:

In 2011, coronary atherosclerosis was one of the top ten most expensive conditions seen during inpatient hospitalizations in the US, with aggregate inpatient hospital costs of $ 10.4 billion.

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In a 2005 report of a study done between 1985 and 1995, it was found that around 87% of aortas and 30% of coronary arteries in age group 5–14 years had fatty streaks which increased with age.

1340:), causing the formation of a thrombus that will rapidly slow or stop blood flow, leading to the death of the tissues fed by the artery in approximately five minutes. This event is called an 772:

via polyunsaturated oils. In another study, rabbits fed heated soybean oil "grossly induced atherosclerosis and marked liver damage were histologically and clinically demonstrated." However,

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secreted by damaged endothelial cells. This causes the formation of a fibrous capsule covering the fatty streak. Intact endothelium can prevent this smooth muscle proliferation by releasing

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Aviram M, Fuhrman B (November 1998). "LDL oxidation by arterial wall macrophages depends on the oxidative status in the lipoprotein and in the cells: role of prooxidants vs. antioxidants".

2046:: calcification of the aortic valve is also frequently observed. These findings link excessive unrepaired DNA damage to premature aging and early atherosclerotic plaque development (see 3863:

Griffin M, Frazer A, Johnson A, Collins P, Owens D, Tomkin GH (June 1998). "Cellular cholesterol synthesis--the relationship to post-prandial glucose and insulin following weight loss".

7813:"Extensive Proliferation of a Subset of Differentiated, yet Plastic, Medial Vascular Smooth Muscle Cells Contributes to Neointimal Formation in Mouse Injury and Atherosclerosis Models" 1914:

of target mRNAs of protein-coding genes, and cause mRNA cleavage or repression of translational machinery. In diseased vascular vessels, miRNAs are dysregulated and highly expressed.

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Velican C, Velican D (March 1985). "Differences in the pattern of atherosclerotic involvement between non-branched regions and adjacent branching points of human coronary arteries".

5395:"Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies" 4008:"Fine particulate air pollution and the progression of carotid intima-medial thickness: a prospective cohort study from the multi-ethnic study of atherosclerosis and air pollution" 1402:

of the lesion breaks, usually at the shoulder of the fibrous cap that separates the lesion from the arterial lumen, where the exposed thrombogenic components of the plaque, mainly

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Apart from thromboembolism, chronically expanding atherosclerotic lesions can cause complete closure of the lumen. Chronically expanding lesions are often asymptomatic until lumen

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Li X, Fang P, Li Y, Kuo YM, Andrews AJ, Nanayakkara G, Johnson C, Fu H, Shan H, Du F, Hoffman NE, Yu D, Eguchi S, Madesh M, Koch WJ, Sun J, Jiang X, Wang H, Yang X (June 2016).

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play a key role in atherogenesis and were historically considered to be beneficial for plaque stability by forming a protective fibrous cap and synthesising strength-giving

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without manipulation of the ascending aorta has demonstrated reduced rates of postoperative stroke and mortality compared to traditional on-pump coronary revascularization.

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Staprãns I, Rapp JH, Pan XM, Hardman DA, Feingold KR (April 1996). "Oxidized lipids in the diet accelerate the development of fatty streaks in cholesterol-fed rabbits".

1154:(EBT) as rings of increased radiographic density, forming halos around the outer edges of the atheromatous plaques, within the artery wall. On CT, >130 units on the 8953: 7077:

Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, van Gils JM, Rayner AJ, Chang AN, Suarez Y, Fernandez-Hernando C, Fisher EA, Moore KJ (July 2011).

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peripheral arterial disease. However, prescription of and adherence to these guideline-concordant therapies is lacking, particularly among young patients and women.

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Borissoff JI, Heeneman S, Kilinç E, Kassák P, Van Oerle R, Winckers K, Govers-Riemslag JW, Hamulyák K, Hackeng TM, Daemen MJ, ten Cate H, Spronk HM (August 2010).

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Atherosclerosis generally starts when a person is young and worsens with age. Almost all people are affected to some degree by the age of 65. It is the number one

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is a late event, which may never occur and is often the result of repeated plaque rupture and healing responses, not just the atherosclerotic process by itself.

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Schwartz CJ, Valente AJ, Sprague EA, Kelley JL, Cayatte AJ, Mowery J (December 1992). "Atherosclerosis. Potential targets for stabilization and regression".

4242:"Polyunsaturated (n-3) fatty acids susceptible to peroxidation are increased in plasma and tissue lipids of rats fed docosahexaenoic acid-containing oils" 1679:

metabolism, may actually promote arterial calcification in the long term despite reducing clot formation in the short term. Also, small molecules such as

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that are present. The muscular portion of artery walls usually remains strong, even after they have remodeled to compensate for the atheromatous plaques.

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Singaraja RR, Stahmer B, Brundert M, Merkel M, Heeren J, Bissada N, Kang M, Timmins JM, Ramakrishnan R, Parks JS, Hayden MR, Rinninger F (August 2006).

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Kratz M, Baars T, Guyenet S (February 2013). "The relationship between high-fat dairy consumption and obesity, cardiovascular, and metabolic disease".

329:, and anticoagulant therapies to reduce the risk of blood clot formation. As the disease state progresses more invasive strategies are applied such as 1419:. The narrowing or obstruction of blood flow can occur in any artery within the body. Obstruction of arteries supplying the heart muscle results in a 1336:. These complications of advanced atherosclerosis are chronic, slowly progressive, and cumulative. Most commonly, soft plaque suddenly ruptures (see 4707:

Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ (May 1987). "Compensatory enlargement of human atherosclerotic coronary arteries".

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content. Under the microscope, the lesion now appears as a fatty streak. Foam cells eventually die and further propagate the inflammatory process.

7988: 8963: 3949:"Carotid intima-media thickness, a marker of subclinical atherosclerosis, and particulate air pollution exposure: the meta-analytical evidence" 2696:"Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study" 2374: 1695:

Cardiovascular disease, which is predominantly the clinical manifestation of atherosclerosis, is one of the leading causes of death worldwide.

1281:'), which is the nodular accumulation of a soft, flaky, yellowish material at the center of large plaques, composed of macrophages nearest the 1221:(blood clot) overlying the atheroma, which obstructs blood flow acutely. With the obstruction of blood flow, downstream tissues are starved of 4587:

Linton MF, Yancey PG, Davies SS, Jerome WG, Linton EF, Song WL, et al. (2000). "The Role of Lipids and Lipoproteins in Atherosclerosis".

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narrowings. Most major blood-flow-stopping events occur at large plaques, which, before their rupture, produced very little if any stenosis.

235:. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. In severe cases, it can result in 4844: 4493:"Oxidized fatty acids promote atherosclerosis only in the presence of dietary cholesterol in low-density lipoprotein receptor knockout mice" 1611:

are widely prescribed for treating atherosclerosis. They have shown benefit in reducing cardiovascular disease and mortality in those with

6867:"Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia" 1050:, and transform into foam cells themselves. A protective fibrous cap normally forms between the fatty deposits and the artery lining (the 8179: 6081:"Vitamin K Supplementation for the Prevention of Cardiovascular Disease: Where Is the Evidence? A Systematic Review of Controlled Trials" 5218:"Preventing heart disease in the 21st century: implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study" 2993: 1954: 1946: 1502:

and diet restrictions. Prevention then is generally by eating a healthy diet, exercising, not smoking, and maintaining a normal weight.

8752: 6249:"G protein-coupled estrogen receptor-1 is involved in the protective effect of protocatechuic aldehyde against endothelial dysfunction" 4180: 4006:

Adar SD, Sheppard L, Vedal S, Polak JF, Sampson PD, Diez Roux AV, Budoff M, Jacobs DR, Barr RG, Watson K, Kaufman JD (April 23, 2013).

2074:, processing of nutrients and production of certain metabolites that can get into blood circulation. One such metabolite, produced by 1983:. Suppression of miR-33 will lead to less cellular cholesterol and higher plasma HDL level through the regulation of ABCA1 expression. 413:

in the coronary arteries, which are responsible for bringing oxygenated blood to the heart, can produce symptoms such as chest pain of

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Berbée JF, Mol IM, Milne GL, Pollock E, Hoeke G, Lütjohann D, Monaco C, Rensen PC, van der Ploeg LH, Shchepinov MS (September 2017).

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Zhao DF, Edelman JJ, Seco M, Bannon PG, Wilson MK, Byrom MJ, Thourani V, Lamy A, Taggart DP, Puskas JD, Vallely MP (February 2017).

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If the heart attack is not fatal, fibrous organization of the clot within the lumen ensues, covering the rupture but also producing

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In 2004, US data indicated that in ~66% of men and ~47% of women, the first symptom of atherosclerotic cardiovascular disease was a

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Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients)

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Enos WF, Holmes RH, Beyer J (1953). "Coronary disease among United States soldiers killed in action in Korea: Preliminary Report".

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Initial damage to the endothelium results in an inflammatory response. Monocytes enter the artery wall from the bloodstream, with

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Wang J, Michelitsch T, Wunderlin A, Mahadeva R (6 April 2009). "Aging as a consequence of misrepair -- A novel theory of aging".

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any evident narrowing of the lumen. Thus, greater attention has been focused on "vulnerable plaque" from the late 1990s onwards.

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that is greater than 75% was considered the hallmark of clinically significant disease in the past because recurring episodes of

696: 341:. Genetic factors are also strongly implicated in the disease process; it is unlikely to be entirely based on lifestyle choices. 317:, exercising, not smoking, and maintaining normal body weight. Treatment of established disease may include medications to lower 7169:"Hepatic ATP-binding cassette transporter A1 is a key molecule in high-density lipoprotein cholesteryl ester metabolism in mice" 4325:

Greco AV, Mingrone G (1990). "Serum and biliary lipid pattern in rabbits feeding a diet enriched with unsaturated fatty acids".

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Spiteller G (November 2005). "The relation of lipid peroxidation processes with atherogenesis: a new theory on atherogenesis".

716: 5801:"Secondary Prevention for Atherosclerotic Cardiovascular Disease: Comparing Recent US and European Guidelines on Dyslipidemia" 8524: 6397: 5518: 4817: 3757: 3082: 2791: 2764: 2358: 7965: 5942:"Sex-Related Disparities in Cardiovascular Health Care Among Patients With Premature Atherosclerotic Cardiovascular Disease" 1174:

Although the disease process tends to be slowly progressive over decades, it usually remains asymptomatic until an atheroma

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Doppler ultrasound of right internal carotid artery with calcified and non-calcified plaques showing less than 70% stenosis

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In 1953, a study was published which examined the results of 300 autopsies performed on U.S. soldiers who had died in the

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in over 50% of children aged 10–14 and 8% had even more advanced lesions with more accumulations of extracellular lipid.

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A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death. Evidence suggests that the

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Changes in diet may help prevent the development of atherosclerosis. Tentative evidence suggests that a diet containing

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basis and indefinitely has generally produced better results, both before and especially after people are symptomatic.

1580: 330: 7761:"Smooth Muscle Cells Contribute the Majority of Foam Cells in ApoE (Apolipoprotein E)-Deficient Mouse Atherosclerosis" 3190:"Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment" 961:, which is selectively required for the differentiation of monocytes to macrophages. The monocytes differentiate into 506:

The atherosclerotic process is not well understood. Atherosclerosis is associated with inflammatory processes in the

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atherosclerotic plaque and can modify their gene expression profile to resemble various other cell types, including

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Early atherosclerotic processes likely begin in childhood. Fibrous and gelatinous lesions have been observed in the

8679: 8296: 5615:"Endothelial (dys)function: the target of physical exercise for prevention and treatment of cardiovascular disease" 2283: 2003: 1962: 1146:

The calcification deposits, after they have become sufficiently advanced, are partially visible on coronary artery

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for decades because the arteries enlarge at all plaque locations, thus there is no effect on blood flow. Even most

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The average age was calculated from the ages of 200 of the soldiers. No age was recorded in nearly 100 of the men.

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Tsukahara, Tamotsu; Tsukahara, Ryoko; Haniu, Hisao; Matsuda, Yoshikazu; Murakami-Murofushi, Kimiko (2015-09-05).

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Rabbits fed atherogenic diets containing various oils were found to undergo the most oxidative susceptibility of

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Wu H, Roks AJ (February 2014). "Genomic instability and vascular aging: a focus on nucleotide excision repair".

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Chen WJ, Yin K, Zhao GJ, Fu YC, Tang CK (June 2012). "The magic and mystery of microRNA-27 in atherosclerosis".

6512: 6173:"Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study" 4936:

Wang-Michelitsch J, Michelitsch TM (2015). "Misrepair mechanism in the development of atherosclerotic plaques".

450:, which supply blood to the kidneys. Plaque occurrence and accumulation lead to decreased kidney blood flow and 8630: 7862:"Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness" 6040:"Coronary Artery Bypass Grafting With and Without Manipulation of the Ascending Aorta: A Network Meta-Analysis" 4360: 3364: 2252: 2198: 1656: 904:. The primary documented driver of this process is oxidized lipoprotein particles within the wall, beneath the 6365: 2169: 8442: 7997: 6558: 2913:

Velican D, Velican C (June 1979). "Study of fibrous plaques occurring in the coronary arteries of children".

2026:, thus linking DNA damage to plaque formation. DNA strand breaks also increased in atherosclerotic plaques. 1094:

The fibro-lipid (fibro-fatty) plaque is characterized by an accumulation of lipid-laden cells underneath the

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Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, et al. (November 2004).

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will raise HDL level and the expression of miR-33 is down-regulated in humans with atherosclerotic plaques.

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is found in cardiovascular diseases. It is involved in atherosclerotic initiation and progression including

514:(LDL) particles. This retention may be a cause, an effect, or both, of the underlying inflammatory process. 8747: 8667: 8372: 6912:

Tsikas D (September 2017). "Combating atherosclerosis with heavy PUFAs: Deuteron not proton is the first".

4742: 4472: 3703:

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is a general term describing any hardening (and loss of elasticity) of medium or large arteries (from

1525:

may improve cardiovascular results. There is also evidence that a Mediterranean diet may be better than a

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The following terms are similar, yet distinct, in both spelling and meaning, and can be easily confused:

1074: 254:

The exact cause of atherosclerosis is unknown and is proposed to be multifactorial. Risk factors include

2437: 1332:

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is the term for techniques that modulate immune system function to suppress this macrophage action.

1359:

of atherosclerosis of the abdominal aorta. Woman of 70 years old with hypertension and dyslipidemia.

1090:

Although arteries are not typically studied microscopically, two plaque types can be distinguished:

302:

limits the flow of oxygen-rich blood to parts of the body. Diagnosis is based upon a physical exam,

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chain reaction in atherogenesis triggered research on the protective role of the heavy isotope (

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gene on chromosome 17. miR-33a/b regulates cholesterol/lipid homeostatis by binding in the

1707: 1399: 1296: 751: 750:) in humans is not clear. Rabbits fed rancid fats develop atherosclerosis faster. Rats fed 571: 531: 462: 307: 7365:"DNA damage-dependent mechanisms of ageing and disease in the macro- and microvasculature" 6963: 6925: 6882: 5718: 5079:

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Microphotography of arterial wall with calcified (violet color) atherosclerotic plaque (

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2712: 2695: 2541: 2030:(WS) is a premature aging condition in humans. WS is caused by a genetic defect in a 1567:

Treatment of established disease may include medications to lower cholesterol such as

388:. These symptoms, however, still vary depending on which artery or organ is affected. 8600: 8549: 8449: 8074: 7942: 7930: 7891: 7842: 7790: 7738: 7689: 7640: 7586: 7529: 7477: 7436: 7384: 7345: 7291: 7240: 7190: 7149: 7108: 7059: 7002: 6967: 6929: 6886: 6847: 6812: 6771: 6730: 6685: 6644: 6636: 6592: 6540: 6532: 6528: 6497: 6485: 6477: 6438: 6430: 6393: 6347: 6288: 6204: 6153: 6112: 6061: 6020: 5971: 5922: 5873: 5822: 5781: 5732: 5683: 5665: 5626: 5595: 5554: 5514: 5487: 5451: 5424: 5367: 5332: 5275: 5239: 5198: 5155: 5110: 5050: 5015: 4974: 4823: 4813: 4806: 4786: 4724: 4689: 4646: 4592: 4566: 4532: 4514: 4441: 4437: 4395: 4342: 4299: 4263: 4222: 4162: 4148: 4083: 4039: 3988: 3929: 3880: 3845: 3804: 3753: 3720: 3685: 3644: 3603: 3599: 3568: 3507: 3458: 3409: 3305: 3270: 3221: 3170: 3120: 3116: 3078: 3043: 2971: 2930: 2926: 2856: 2787: 2760: 2739: 2727: 2676: 2545: 2502: 2494: 2354: 1990:, removed cholesterol that had built up in the arteries of mice fed a high-fat diet. 1980: 1699: 1530: 1499: 1337: 1100: 970: 909: 664: 649: 536: 404: 392: 369: 303: 77: 8053: 7014: 6898: 5908: 5287: 5062: 4453: 4407: 4062:"Biological gradient between long-term arsenic exposure and carotid atherosclerosis" 3470: 3317: 2808:"Evolutionary gene loss may help explain why only humans are prone to heart attacks" 2514: 1887:(D-PUFAs) that are less prone to oxidation than ordinary PUFAs (H-PUFAs). PUFAs are 8605: 8254: 8157: 7922: 7881: 7873: 7832: 7824: 7780: 7772: 7728: 7720: 7679: 7671: 7630: 7622: 7576: 7568: 7519: 7511: 7467: 7426: 7396: 7376: 7335: 7325: 7312:

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in bringing about long-term changes to cardiovascular risk factors (e.g., lower

1423:, while the obstruction of arteries supplying the brain results in an ischaemic 1363: 780:, or oxidized cholesterols, from fried foods and smoking, that are the culprit. 8846: 8696: 8559: 8519: 8454: 8415: 8326: 7776: 7572: 7211:"Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming" 7045: 6662:

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in the body, can contribute to atherosclerosis in many ways: modulation of the

1752: 1534: 1267: 1127:), precipitates of calcium (hematoxylinophilic), and rarely, lipid-laden cells. 1017: 818: 720: 679: 674: 669: 454:, which, like in all other areas, is typically asymptomatic until late stages. 429:—the heart beating either too slowly or too quickly—are another consequence of 372:

do not produce symptoms until enough narrowing or closure of an artery, due to

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Examples of anatomical detection methods include coronary calcium scoring by

1206: 1095: 1043: 1008: 989: 981: 965:, which proliferate locally, ingest oxidized LDL, slowly turning into large " 826: 773: 762: 654: 634: 622: 617: 8541: 8038: 7311: 6148: 6131: 4827: 4218: 3256: 3061:

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In 1992, a report had shown that microscopic fatty streaks were seen in the

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Early atherogenesis is characterized by the adherence of blood circulating

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The relation between dietary fat and atherosclerosis is controversial. The

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Calcification at the outer base of older or more advanced

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The progression of atherosclerosis (narrowing exaggerated)

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Koh KK, Han SH, Oh PC, Shin EK, Quon MJ (April 2010).

4423: 4204: 4110:"Treating Hypothyroidism Reduces Atherosclerosis Risk" 4005: 1258:

The plaque is divided into three distinct components:

731:) recommends much higher levels of fat, especially of 6864: 6723:"Costs for Hospital Stays in the United States, 2011" 6037: 5839: 2987: 2985: 1655:

can reopen narrowed arteries and improve blood flow.

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Progression of atherosclerosis to late complications

182:, exercise, not smoking, maintaining a normal weight 7801: 6720: 6129: 5619:

The Journal of Sports Medicine and Physical Fitness

3824:"Need to test the arterial inflammation hypothesis" 3536: 1961:of genes involved in cholesterol transport such as 1785:is a hardening of an artery specifically due to an 1675:, which inhibit clot formation by interfering with 1454:Besides the traditional diagnostic methods such as 1099:muscle cells) with elevated tissue cholesterol and 837:. The bulk of these lesions is made of excess fat, 7765:Arteriosclerosis, Thrombosis, and Vascular Biology 7314:"DNA Damage: A Main Determinant of Vascular Aging" 7173:Arteriosclerosis, Thrombosis, and Vascular Biology 6795:Arteriosclerosis, Thrombosis, and Vascular Biology 6788: 6455: 6136:Arteriosclerosis, Thrombosis, and Vascular Biology 6130:Price PA, Faus SA, Williamson MK (February 2000). 5939: 5532: 5530: 4998:Arteriosclerosis, Thrombosis, and Vascular Biology 4805: 4207:Arteriosclerosis, Thrombosis, and Vascular Biology 4130: 3245:Arteriosclerosis, Thrombosis, and Vascular Biology 3145:Arteriosclerosis, Thrombosis, and Vascular Biology 2982: 829:, a region of the vessel wall located between the 522:less compliant to stretching with each heartbeat. 421:, dizziness or lightheadedness, breathlessness or 7911:"Vascular smooth muscle cells in atherosclerosis" 7660:"Vascular Smooth Muscle Cells in Atherosclerosis" 7657: 5349: 5209: 4240:Song JH, Fujimoto K, Miyazawa T (December 2000). 3856: 3377: 2899:. National Heart, Lung and Blood Institute. 2011. 1575:, or medications that decrease clotting, such as 8954:Diseases of arteries, arterioles and capillaries 8945: 7408: 7406: 7307: 7305: 7027: 6721:Pfuntner A, Wier LM, Steiner C (December 2013). 5897:Circulation: Cardiovascular Quality and Outcomes 5643: 5392: 5216:McGill HC, McMahan CA, Gidding SS (March 2008). 2891: 2889: 2887: 2759:. Lippincott Williams & Wilkins. p. 2. 2619: 2595:"How Is Atherosclerosis Diagnosed? - NHLBI, NIH" 1833:(HDL) on atherosclerosis has been with the rare 1240: 789:keep them cool and in oxygen-free environments. 758:systems, and accumulated significant amounts of 719:make similar recommendations. In contrast, Prof 7658:Bennett MR, Sinha S, Owens GK (February 2016). 7608: 7546: 7497: 6789:Nilsson J, Hansson GK, Shah PK (January 2005). 5527: 4582: 4580: 4059: 3102: 2693: 2229:DAIC (Diagnostic and Interventional Cardiology) 2089: 1930:, cell type progression and proliferation, and 876:showing significant atherosclerosis and marked 776:claims that it is not dietary cholesterol, but 7493: 7491: 7456:"Role of DNA damage in cardiovascular disease" 6945: 6943: 4131:Bale BF, Doneen AL, Vigerust DJ (April 2017). 3744:. 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Heart and Stroke Foundation. 2965: 2721: 2711: 2670: 2488: 2271: 2188: 2153: 1698:Almost all children older than age 10 in 880:narrowing. Tissue has been stained using 7754: 7752: 7609:Harman JL, Jørgensen HF (October 2019). 6782: 6382: 2824: 2342: 2340: 2302: 1607:The group of medications referred to as 1554:help to prevent clots, and a variety of 1429: 1362: 1351: 1288:Underlying areas of cholesterol crystals 1165: 1073: 860: 497: 313:Prevention guidelines include, eating a 58:Arteriosclerotic vascular disease (ASVD) 7125: 7028:Bommer GT, MacDougald OA (March 2011). 6832:Molecular Nutrition & Food Research 5988: 5536: 5069: 4994:"Concept of vulnerable/unstable plaque" 4812:. Englewood Cliffs, NJ: Prentice Hall. 3378:Campbell LA, Rosenfeld ME (July 2015). 3132: 2438:"What Is Atherosclerosis? - NHLBI, NIH" 2010:, a common type of oxidative damage in 1161: 517:The presence of the plaque induces the 407:and strokes equally affect both sexes. 14: 8946: 7273: 6911: 6582: 4700: 4663: 4377: 4233: 3490:The Indian Journal of Medical Research 3063:"Atherosclerotic Burden and Mortality" 2773: 2396: 2394: 926:and become oxidized, creating risk of 845:. At first, as the plaques grow, only 717:National Cholesterol Education Program 611: 18:Atherosclerotic cardiovascular disease 8964:Medical conditions related to obesity 8525:Hereditary hemorrhagic telangiectasia 8161: 7749: 7363:Shah AV, Bennett MR (December 2017). 7083:The Journal of Clinical Investigation 6964:10.1016/j.atherosclerosis.2012.01.020 6926:10.1016/j.atherosclerosis.2017.07.018 6883:10.1016/j.atherosclerosis.2017.06.916 6559:"Stopping Heart Disease in Childhood" 5991:"Questioning the benefits of statins" 5719:10.1016/j.atherosclerosis.2009.09.007 4318: 4274: 3815: 3019:Sims NR, Muyderman H (January 2010). 2337: 2253:"Who Is at Risk for Atherosclerosis?" 1415:supply to nearby cells, resulting in 984:proliferation and migration from the 359: 8530:Generalized essential telangiectasia 6510: 5300: 5128:Stary HC, Chandler AB, Dinsmore RE, 4956: 4851:. September 29, 2014. Archived from 4537:The Lecturio Medical Concept Library 3427:Sinha A, Feinstein MJ (March 2019). 3096: 2830: 2779: 2527: 2469:Molecular and Cellular Endocrinology 2347:Aronow WS, Fleg JL, Rich MW (2013). 765:in their blood, livers and kidneys. 294:, and other substances found in the 7255:"A sugar can melt away cholesterol" 6754:The New England Journal of Medicine 6415:Journal of Atherosclerosis Research 4959:The New England Journal of Medicine 4709:The New England Journal of Medicine 3705:The New England Journal of Medicine 3365:"Atherosclerosis | NHLBI, NIH" 3290:Molecular and Cellular Biochemistry 2756:Textbook of Cardiovascular Medicine 2391: 2014:, is found to accumulate in plaque 1941:miR-33a and miR-33b are located on 1870:Immunomodulation of atherosclerosis 1217:. The result is the formation of a 1069: 607:Coronary anatomy and branch pattern 417:and shortness of breath, sweating, 24: 7432:10.1161/01.cir.0000026393.47805.21 7186:10.1161/01.ATV.0000229219.13757.a2 6808:10.1161/01.ATV.0000149142.42590.a2 5194:10.1161/01.CIR.0000070585.48035.D1 4079:10.1161/01.cir.0000015862.64816.b2 3841:10.1161/01.CIR.0000021112.29409.A2 3433:The Canadian Journal of Cardiology 1581:percutaneous coronary intervention 1190:caps that have become "unstable". 896:) to the vascular bed lining, the 792: 746:The role of eating oxidized fats ( 723:(Harvard School of Public Health, 331:percutaneous coronary intervention 25: 8980: 7953: 7276:Trends in Cardiovascular Medicine 6229:from the original on 7 April 2010 5818:10.1161/CIRCULATIONAHA.119.044282 5572:Ambrose JA, Barua RS (May 2004). 5505:Paul P, Williams B, eds. 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Abnormal heart rhythms called 7615:British Journal of Pharmacology 7253:Hesman Saey T (April 8, 2016). 6511:Enos, William F. 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If this is the 1135:just large enough to hold the 1078:Severe atherosclerosis of the 849:occurs without any narrowing. 13: 1: 8443:Aneurysm of sinus of Valsalva 8297:Monckeberg's arteriosclerosis 7829:10.1161/CIRCRESAHA.116.309799 7676:10.1161/CIRCRESAHA.115.306361 6987:Current Opinion in Lipidology 6427:10.1016/S0368-1319(69)80020-7 5352:European Journal of Nutrition 5097:10.1161/CIRCRESAHA.115.306247 4392:10.1016/j.physbeh.2005.08.058 4339:10.1016/S0232-1513(11)80281-1 3877:10.1016/S0021-9150(98)00036-7 3555:10.1161/CIRCRESAHA.119.315644 2713:10.1016/S2214-109X(20)30117-0 2542:10.1016/s0021-9150(03)00012-1 2146: 1993: 1829:An indication of the role of 1493: 1253: 1241:Accelerated growth of plaques 953:induction of factors such as 934:, involving enzymes (such as 713:American Diabetes Association 525: 8748:Chronic venous insufficiency 8373:Aortoiliac occlusive disease 7381:10.1016/j.ejphar.2017.03.050 7227:10.1126/scitranslmed.aad6100 6999:10.1097/MOL.0b013e3283534c9f 6681:10.1016/j.precon.2005.02.010 6366:"The top 10 causes of death" 6333:10.1371/journal.pone.0149394 6274:10.1371/journal.pone.0113242 5958:10.1001/jamacardio.2021.0683 5484:10.1016/j.amjmed.2011.04.024 4473:Food and Drug Administration 4137:Postgraduate Medical Journal 4025:10.1371/journal.pmed.1001430 3974:10.1371/journal.pone.0127014 3600:10.1016/0021-9150(85)90126-1 3396:10.1016/j.arcmed.2015.05.006 3075:10.1007/978-0-387-78665-0_51 3040:10.1016/j.bbadis.2009.09.003 2927:10.1016/0021-9150(79)90117-5 2753:Topol EJ, Califf RM (2007). 2095:Vascular smooth muscle cells 2090:Vascular smooth muscle cells 2034:that is employed in several 1811: 1734: 1667:There is evidence that some 1643:, surgery may be indicated. 1585:coronary artery bypass graft 1562: 1347: 335:coronary artery bypass graft 219:is a pattern of the disease 7: 8763:Inferior vena cava syndrome 8758:Superior vena cava syndrome 8485:Vertebral artery dissection 8475:Intracranial berry aneurysm 4971:10.1056/NEJM199901143400207 4721:10.1056/NEJM198705283162204 1885:polyunsaturated fatty acids 1819: 1762: 'artery' and 1710:fatty streaks beginning in 1540: 1379:Areas of severe narrowing, 1266:("lump of gruel", from 856: 472:of U.S. soldiers killed in 468:Case studies have included 256:abnormal cholesterol levels 10: 8985: 8864:Hypertensive heart disease 8515:Arteriovenous malformation 8490:Familial aortic dissection 7915:Nature Reviews. Cardiology 7777:10.1161/ATVBAHA.119.312434 7573:10.1038/s41467-017-00900-1 7504:Nature Reviews. Cardiology 7046:10.1016/j.cmet.2011.02.004 6708:Merriam-Webster Dictionary 6057:10.1016/j.jacc.2016.11.071 5859:10.1016/j.jacc.2018.11.003 5591:10.1016/j.jacc.2003.12.047 5011:10.1161/ATVBAHA.108.179739 4120:(3): 656. 1 February 2004. 3445:10.1016/j.cjca.2018.11.029 3157:10.1161/ATVBAHA.115.306964 2663:10.1016/j.jacc.2020.11.010 2581:10.1016/j.cjca.2023.09.009 2419:10.1016/j.cjca.2023.09.009 2353:. 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Global Health 2481:10.1016/j.mce.2015.05.021 1824: 1800: 'gruel'). The term 1641:peripheral artery disease 1573:blood pressure medication 1237:(heart attack) develops. 707:from total calories. The 327:blood pressure medication 245:peripheral artery disease 206: 197:blood pressure medication 186: 175: 142: 134: 126: 117:peripheral artery disease 102: 92: 76: 71: 62: 54: 49: 39:Atherosclerosis (journal) 8874:Hypertensive nephropathy 8687:Post-thrombotic syndrome 8668:Paget–Schroetter disease 8460:Coronary artery aneurysm 8438:Thoracic aortic aneurysm 7473:10.1253/circj.CJ-13-1194 7126:Iwakiri Y (March 2012). 6474:10.1080/pdp.21.2.213.237 6177:The Journal of Nutrition 5151:10.1161/01.CIR.92.5.1355 4894:10.1038/npre.2009.2988.2 4808:Human Biology and Health 4782:10.1093/eurheartj/ehv653 4497:The Journal of Nutrition 4246:The Journal of Nutrition 2118: 1898: 1831:high-density lipoprotein 1747:, and atherosclerosis. 1662: 1472:intravascular ultrasound 1233:(cardiac chest pain) or 1152:electron beam tomography 1029:high-density lipoprotein 1004:Calcification and lipids 378:cardiovascular disorders 210:≈100% (>65 years old) 130:Youth (worsens with age) 30:Not to be confused with 8929:Orthostatic hypotension 8911:White coat hypertension 8388:Fibromuscular dysplasia 8352:Carotid artery stenosis 7983:considered for deletion 7866:Cardiovascular Research 6390:Robbins Basic Pathology 6149:10.1161/01.ATV.20.2.317 4745:. www.pathologyatlas.ro 4219:10.1161/01.atv.16.4.533 3627:Cardiovascular Research 3302:10.1023/A:1006841011201 3257:10.1161/01.ATV.15.5.551 2967:10.1161/01.CIR.38.5.859 1685:protocatechuic aldehyde 1645:Vascular bypass surgery 1505: 1468:intimal media thickness 1025:low-density lipoprotein 920:Low-density lipoprotein 817:of the artery lumen in 512:low-density lipoprotein 401:coronary artery disease 260:inflammatory biomarkers 237:coronary artery disease 109:Coronary artery disease 8901:Pulmonary hypertension 8884:Secondary hypertension 8879:Essential hypertension 8869:Hypertensive emergency 8710:Portacaval anastomosis 8646:Portal vein thrombosis 8288:Critical limb ischemia 8189:Cardiovascular disease 7964:Quotations related to 6844:10.1002/mnfr.200500055 6727:HCUP Statistical Brief 6190:10.1093/jn/134.11.3100 5650:Cardiology and Therapy 4769:European Heart Journal 4565:(6 Suppl): III117–23. 4510:10.1093/jn/132.11.3256 4327:Experimental Pathology 4259:10.1093/jn/130.12.3028 3791:10.1093/ajcn/80.5.1175 2112:mesenchymal stem cells 2080:trimethylamine N-oxide 2016:vascular smooth muscle 1589:carotid endarterectomy 1516:cardiovascular disease 1435: 1393:cardiovascular disease 1376: 1360: 1171: 1087: 1013:vascular smooth muscle 928:cardiovascular disease 885: 813:, begin to attack the 503: 452:chronic kidney disease 339:carotid endarterectomy 8906:Systolic hypertension 8651:Renal vein thrombosis 8510:Arteriovenous fistula 8502:Vascular malformation 8470:Intracranial aneurysm 8357:Renal artery stenosis 7553:Nature Communications 7145:10.4161/cc.11.6.19744 6767:10.1056/NEJMoa0706628 5551:10.3949/ccjm.70.5.431 4468:"Dietary Supplements" 3916:10.1001/jama.2008.867 3717:10.1056/NEJMra1011670 1681:3-hydroxybenzaldehyde 1446:and abnormalities in 1433: 1366: 1355: 1235:myocardial infarction 1215:system of coagulation 1180:myocardial infarction 1169: 1077: 864: 640:Systemic inflammation 600:Genetic abnormalities 501: 258:, elevated levels of 37:For the journal, see 8820:Paradoxical embolism 8815:Cholesterol embolism 8641:May–Thurner syndrome 8636:Budd–Chiari syndrome 8619:Deep vein thrombosis 8614:primarily lower limb 8393:Raynaud's phenomenon 7817:Circulation Research 7664:Circulation Research 7331:10.3390/ijms17050748 6007:10.1503/cmaj.1050120 5085:Circulation Research 3543:Circulation Research 2099:extracellular matrix 1963:ATP binding cassette 1773: 'hardening'); 1706:fatty streaks, with 1400:extracellular matrix 1297:extracellular matrix 1162:Rupture and stenosis 942:in the endothelium. 799:atheromatous plaques 729:Nurses' Health Study 572:Bacterial infections 532:Western pattern diet 463:sudden cardiac death 308:exercise stress test 233:atheromatous plaques 8896:Benign hypertension 7565:2017NatCo...8..845J 7460:Circulation Journal 6324:2016PLoSO..1149394K 6265:2014PLoSO...9k3242K 5539:Cleve. Clin. J. Med 4855:on 24 February 2015 4678:2013NatMa..12..476M 4187:on 26 December 2007 3965:2015PLoSO..1027014P 2845:1993Natur.362..801R 2006:in vascular aging. 1928:glucose homeostatis 1889:essential nutrients 1787:atheromatous plaque 1700:developed countries 1301:smooth muscle cells 1182:or "heart attack". 1148:computed tomography 973:and resulting high 737:polyunsaturated fat 685:Periodontal disease 660:Sedentary lifestyle 612:Lesser or uncertain 444:Peripheral arteries 364:Atherosclerosis is 354:developed countries 298:. The narrowing of 286:is made up of fat, 264:high blood pressure 149:High blood pressure 8810:Pulmonary embolism 8720:Esophageal varices 8658:upper limb / torso 8302:Arteriolosclerosis 8101:External resources 7878:10.1093/cvr/cvy010 7725:10.1038/nmeth.2332 6563:NutritionFacts.org 6098:10.3390/nu12102909 4476:. 4 February 2020. 4296:10.1007/BF02536616 3640:10.1093/cvr/cvp066 2626:Genes and Disease 1877:lipid peroxidation 1781:(small arteries); 1775:arteriolosclerosis 1745:arteriolosclerosis 1523:Mediterranean diet 1436: 1377: 1361: 1172: 1088: 886: 882:Masson's trichrome 872:that supplies the 542:Insulin resistance 504: 360:Signs and symptoms 8959:Vascular diseases 8941: 8940: 8937: 8936: 8781:Arteries or veins 8776: 8775: 8601:Venous thrombosis 8568: 8567: 8550:Cherry hemangioma 8450:Aortic dissection 8401: 8400: 8236:Buerger's disease 8155: 8154: 7823:(12): 1313–1323. 7627:10.1111/bph.14779 7621:(19): 3741–3753. 6627:(sup1): 51S–54S. 6523:(12): 1090–1093. 6398:978-1-4160-2973-1 6183:(11): 3100–3105. 5869:20.500.12749/1738 5852:(24): e285–e350. 5811:(14): 1121–1123. 5520:978-0-7817-9989-8 5411:10.1136/bmj.g4490 4876:Nature Precedings 4849:www.nhlbi.nih.gov 4819:978-0-13-981176-0 4533:"Atherosclerosis" 4503:(11): 3256–3262. 4491:(November 2002). 4365:medicalxpress.com 4143:(1098): 215–220. 4072:(15): 1804–1809. 3759:978-0-309-08525-0 3084:978-0-387-78665-0 2897:"Atherosclerosis" 2793:978-1-84628-810-4 2766:978-0-7817-7012-5 2657:(25): 2982–3021. 2622:"Atherosclerosis" 2599:www.nhlbi.nih.gov 2575:(12): 1781–1794. 2442:www.nhlbi.nih.gov 2413:(12): 1781–1794. 2360:978-1-84214-544-9 2323:www.nhlbi.nih.gov 2288:www.nhlbi.nih.gov 2257:www.nhlbi.nih.gov 2203:www.nhlbi.nih.gov 2174:www.nhlbi.nih.gov 2040:coronary arteries 2024:endothelial cells 1953:and intron 17 of 1924:insulin signaling 1531:cholesterol level 1500:smoking cessation 1338:vulnerable plaque 1213:and activate the 1101:cholesterol ester 665:Arsenic poisoning 650:Sleep deprivation 537:Abdominal obesity 508:endothelial cells 405:cerebral arteries 393:coronary arteries 304:electrocardiogram 274:(both active and 214: 213: 44:Medical condition 16:(Redirected from 8976: 8852: 8851: 8663:Mondor's disease 8606:Thrombophlebitis 8579: 8578: 8255:Arteriosclerosis 8251: 8250: 8212: 8211: 8182: 8175: 8168: 8159: 8158: 8005: 8004: 7986: 7963: 7947: 7946: 7906: 7900: 7899: 7889: 7857: 7851: 7850: 7840: 7808: 7799: 7798: 7788: 7756: 7747: 7746: 7736: 7704: 7698: 7697: 7687: 7655: 7649: 7648: 7638: 7606: 7595: 7594: 7584: 7544: 7538: 7537: 7527: 7495: 7486: 7485: 7475: 7451: 7445: 7444: 7434: 7410: 7401: 7400: 7360: 7354: 7353: 7343: 7333: 7309: 7300: 7299: 7271: 7265: 7262: 7259:Science News.org 7251:Lay summary in: 7248: 7238: 7221:(333): 333ra50. 7205: 7199: 7198: 7188: 7164: 7158: 7157: 7147: 7123: 7117: 7116: 7106: 7095:10.1172/JCI57275 7074: 7068: 7067: 7057: 7025: 7019: 7018: 6982: 6976: 6975: 6947: 6938: 6937: 6909: 6903: 6902: 6862: 6856: 6855: 6838:(11): 999–1013. 6827: 6821: 6820: 6810: 6786: 6780: 6779: 6769: 6745: 6739: 6738: 6718: 6712: 6711: 6700: 6694: 6693: 6683: 6659: 6653: 6652: 6612: 6606: 6605: 6604: 6603: 6580: 6574: 6573: 6571: 6570: 6555: 6549: 6548: 6508: 6502: 6501: 6453: 6447: 6446: 6406: 6400: 6386: 6380: 6379: 6377: 6376: 6362: 6356: 6355: 6345: 6335: 6303: 6297: 6296: 6286: 6276: 6244: 6238: 6237: 6235: 6234: 6219: 6213: 6212: 6202: 6192: 6168: 6162: 6161: 6151: 6127: 6121: 6120: 6110: 6100: 6076: 6070: 6069: 6059: 6035: 6029: 6028: 6018: 5986: 5980: 5979: 5969: 5937: 5931: 5930: 5920: 5888: 5882: 5881: 5871: 5861: 5837: 5831: 5830: 5820: 5796: 5790: 5789: 5779: 5747: 5741: 5740: 5730: 5698: 5692: 5691: 5681: 5641: 5635: 5634: 5610: 5604: 5603: 5593: 5569: 5563: 5562: 5534: 5525: 5524: 5502: 5496: 5495: 5478:(9): 841–51.e2. 5466: 5460: 5459: 5439: 5433: 5432: 5422: 5390: 5384: 5383: 5347: 5341: 5340: 5330: 5301:Rice BH (2014). 5298: 5292: 5291: 5254: 5248: 5247: 5237: 5213: 5207: 5206: 5196: 5170: 5164: 5163: 5153: 5144:(5): 1355–1374. 5125: 5119: 5118: 5108: 5076: 5067: 5066: 5030: 5024: 5023: 5013: 4989: 4983: 4982: 4954: 4948: 4947: 4945: 4933: 4927: 4926: 4924: 4912: 4906: 4905: 4887: 4871: 4865: 4864: 4862: 4860: 4841: 4832: 4831: 4811: 4801: 4795: 4794: 4784: 4760: 4754: 4753: 4751: 4750: 4739: 4733: 4732: 4704: 4698: 4697: 4686:10.1038/nmat3663 4666:Nature Materials 4661: 4655: 4654: 4644: 4611: 4605: 4604: 4584: 4575: 4574: 4554: 4548: 4547: 4545: 4543: 4529: 4523: 4522: 4512: 4484: 4478: 4477: 4464: 4458: 4457: 4421: 4415: 4414: 4375: 4369: 4368: 4357: 4351: 4350: 4322: 4316: 4315: 4278: 4272: 4271: 4261: 4237: 4231: 4230: 4202: 4196: 4195: 4193: 4192: 4183:. Archived from 4177: 4171: 4170: 4160: 4128: 4122: 4121: 4106: 4100: 4099: 4081: 4057: 4051: 4050: 4037: 4027: 4003: 3997: 3996: 3986: 3976: 3944: 3938: 3937: 3927: 3895: 3889: 3888: 3860: 3854: 3853: 3843: 3819: 3813: 3812: 3802: 3770: 3764: 3763: 3735: 3729: 3728: 3700: 3694: 3693: 3683: 3659: 3653: 3652: 3642: 3618: 3612: 3611: 3583: 3577: 3576: 3566: 3534: 3528: 3522: 3516: 3515: 3505: 3481: 3475: 3474: 3456: 3424: 3418: 3417: 3407: 3375: 3369: 3368: 3367:. 24 March 2022. 3361: 3322: 3321: 3285: 3279: 3278: 3268: 3236: 3230: 3229: 3219: 3209: 3185: 3179: 3178: 3168: 3136: 3130: 3128: 3100: 3094: 3093: 3092: 3091: 3058: 3052: 3051: 3025: 3016: 3010: 3008: 3006: 3005: 2996:. Archived from 2989: 2980: 2979: 2969: 2945: 2939: 2938: 2910: 2901: 2900: 2893: 2882: 2879: 2873: 2872: 2853:10.1038/362801a0 2828: 2822: 2821: 2819: 2818: 2804: 2798: 2797: 2777: 2771: 2770: 2750: 2744: 2743: 2725: 2715: 2706:(5): e721–e729. 2691: 2685: 2684: 2674: 2642: 2636: 2635: 2634: 2633: 2617: 2611: 2610: 2608: 2606: 2591: 2585: 2584: 2560: 2554: 2553: 2525: 2519: 2518: 2492: 2460: 2454: 2453: 2451: 2449: 2434: 2423: 2422: 2398: 2389: 2388: 2386: 2385: 2371: 2365: 2364: 2344: 2335: 2334: 2332: 2330: 2315: 2300: 2299: 2297: 2295: 2280: 2269: 2268: 2266: 2264: 2249: 2240: 2239: 2237: 2236: 2221: 2215: 2214: 2212: 2210: 2195: 2186: 2185: 2183: 2181: 2166: 2140: 2129: 1974:or converted to 1920:lipid metabolism 1749:Arteriosclerosis 1741:arteriosclerosis 1651:with or without 1613:high cholesterol 1556:antihypertensive 1383:, detectable by 1209:; they activate 1156:Hounsfield scale 1070:Visible features 894:white blood cell 645:Hyperinsulinemia 437:Carotid arteries 411:Marked narrowing 310:, among others. 290:, immune cells, 249:kidney disorders 221:arteriosclerosis 67: 47: 46: 32:Arteriosclerosis 21: 8984: 8983: 8979: 8978: 8977: 8975: 8974: 8973: 8944: 8943: 8942: 8933: 8915: 8841: 8798:Microangiopathy 8793:Macroangiopathy 8772: 8736: 8705:Gastric varices 8691: 8604: 8595: 8564: 8536: 8496: 8428:Aortic aneurysm 8414: 8397: 8383:Erythromelalgia 8361: 8338: 8263:Atherosclerosis 8240: 8204: 8192: 8186: 8156: 8151: 8150: 8137:Atherosclerosis 8096: 8095: 8016: 7998:Atherosclerosis 7989:Atherosclerosis 7971: 7966:Atherosclerosis 7956: 7951: 7950: 7921:(12): 727–744. 7907: 7903: 7858: 7854: 7809: 7802: 7757: 7750: 7705: 7701: 7656: 7652: 7607: 7598: 7545: 7541: 7510:(12): 699–700. 7496: 7489: 7452: 7448: 7411: 7404: 7361: 7357: 7310: 7303: 7272: 7268: 7252: 7206: 7202: 7165: 7161: 7124: 7120: 7075: 7071: 7034:Cell Metabolism 7026: 7022: 6983: 6979: 6952:Atherosclerosis 6948: 6941: 6914:Atherosclerosis 6910: 6906: 6871:Atherosclerosis 6863: 6859: 6828: 6824: 6787: 6783: 6760:(21): 2109–22. 6746: 6742: 6719: 6715: 6702: 6701: 6697: 6660: 6656: 6613: 6609: 6601: 6599: 6581: 6577: 6568: 6566: 6557: 6556: 6552: 6509: 6505: 6454: 6450: 6407: 6403: 6387: 6383: 6374: 6372: 6364: 6363: 6359: 6318:(3): e0149394. 6304: 6300: 6259:(11): e113242. 6245: 6241: 6232: 6230: 6221: 6220: 6216: 6169: 6165: 6128: 6124: 6077: 6073: 6036: 6032: 5987: 5983: 5946:JAMA Cardiology 5938: 5934: 5889: 5885: 5838: 5834: 5797: 5793: 5762:(1): CD004816. 5748: 5744: 5707:Atherosclerosis 5699: 5695: 5642: 5638: 5611: 5607: 5570: 5566: 5535: 5528: 5521: 5503: 5499: 5467: 5463: 5440: 5436: 5391: 5387: 5348: 5344: 5299: 5295: 5255: 5251: 5214: 5210: 5187:(16): 2068–71. 5171: 5167: 5126: 5122: 5077: 5070: 5031: 5027: 4990: 4986: 4955: 4951: 4934: 4930: 4913: 4909: 4872: 4868: 4858: 4856: 4843: 4842: 4835: 4820: 4802: 4798: 4775:(25): 1959–67. 4761: 4757: 4748: 4746: 4741: 4740: 4736: 4705: 4701: 4662: 4658: 4633:10.1038/nm.3258 4621:Nature Medicine 4612: 4608: 4585: 4578: 4555: 4551: 4541: 4539: 4531: 4530: 4526: 4489:Parthasarathy S 4485: 4481: 4466: 4465: 4461: 4422: 4418: 4376: 4372: 4359: 4358: 4354: 4323: 4319: 4290:(12): 1145–50. 4279: 4275: 4252:(12): 3028–33. 4238: 4234: 4203: 4199: 4190: 4188: 4179: 4178: 4174: 4129: 4125: 4108: 4107: 4103: 4058: 4054: 4018:(4): e1001430. 4004: 4000: 3959:(5): e0127014. 3945: 3941: 3910:(24): 2859–66. 3896: 3892: 3865:Atherosclerosis 3861: 3857: 3820: 3816: 3771: 3767: 3760: 3736: 3732: 3711:(18): 1746–60. 3701: 3697: 3660: 3656: 3619: 3615: 3588:Atherosclerosis 3584: 3580: 3535: 3531: 3523: 3519: 3482: 3478: 3425: 3421: 3376: 3372: 3363: 3362: 3325: 3296:(1–2): 149–59. 3286: 3282: 3237: 3233: 3186: 3182: 3151:(6): 1090–100. 3137: 3133: 3111:(12): 1090–93. 3101: 3097: 3089: 3087: 3085: 3059: 3055: 3023: 3017: 3013: 3003: 3001: 2992: 2990: 2983: 2946: 2942: 2915:Atherosclerosis 2911: 2904: 2895: 2894: 2885: 2880: 2876: 2839:(6423): 801–9. 2829: 2825: 2816: 2814: 2806: 2805: 2801: 2794: 2780:Shor A (2008). 2778: 2774: 2767: 2751: 2747: 2692: 2688: 2643: 2639: 2631: 2629: 2618: 2614: 2604: 2602: 2593: 2592: 2588: 2561: 2557: 2530:Atherosclerosis 2526: 2522: 2461: 2457: 2447: 2445: 2436: 2435: 2426: 2399: 2392: 2383: 2381: 2373: 2372: 2368: 2361: 2345: 2338: 2328: 2326: 2317: 2316: 2303: 2293: 2291: 2282: 2281: 2272: 2262: 2260: 2251: 2250: 2243: 2234: 2232: 2231:. 27 April 2015 2223: 2222: 2218: 2208: 2206: 2197: 2196: 2189: 2179: 2177: 2168: 2167: 2154: 2149: 2144: 2143: 2130: 2126: 2121: 2092: 2056: 2028:Werner syndrome 1996: 1901: 1893:transgenic mice 1875:Involvement of 1864:The actions of 1827: 1822: 1814: 1783:atherosclerosis 1737: 1693: 1671:, particularly 1665: 1639:in the case of 1629: 1605: 1565: 1543: 1508: 1496: 1488:nuclear imaging 1466:, carotid IMT ( 1406:, will trigger 1350: 1322:thromboembolism 1256: 1247:amyloid plaques 1243: 1229:(heart muscle) 1164: 1072: 1006: 992:in response to 951:redox signaling 859: 847:wall thickening 795: 793:Pathophysiology 733:monounsaturated 693: 614: 585: 567:Tobacco smoking 528: 496: 494:Lipoprotein (a) 486: 370:plaque ruptures 362: 276:passive smoking 217:Atherosclerosis 121:kidney problems 50:Atherosclerosis 45: 42: 35: 28: 23: 22: 15: 12: 11: 5: 8982: 8972: 8971: 8966: 8961: 8956: 8939: 8938: 8935: 8934: 8932: 8931: 8925: 8923: 8917: 8916: 8914: 8913: 8908: 8903: 8898: 8893: 8892: 8891: 8881: 8876: 8871: 8866: 8860: 8858: 8849: 8847:Blood pressure 8843: 8842: 8840: 8839: 8834: 8829: 8824: 8823: 8822: 8817: 8812: 8802: 8801: 8800: 8795: 8784: 8782: 8778: 8777: 8774: 8773: 8771: 8770: 8765: 8760: 8755: 8750: 8744: 8742: 8738: 8737: 8735: 8734: 8729: 8728: 8727: 8722: 8717: 8707: 8701: 8699: 8697:Varicose veins 8693: 8692: 8690: 8689: 8684: 8683: 8682: 8672: 8671: 8670: 8665: 8655: 8654: 8653: 8648: 8643: 8638: 8633: 8623: 8622: 8621: 8610: 8608: 8597: 8596: 8594: 8593: 8587: 8585: 8576: 8570: 8569: 8566: 8565: 8563: 8562: 8560:Spider angioma 8557: 8552: 8546: 8544: 8542:Vascular nevus 8538: 8537: 8535: 8534: 8533: 8532: 8527: 8520:Telangiectasia 8517: 8512: 8506: 8504: 8498: 8497: 8495: 8494: 8493: 8492: 8487: 8482: 8477: 8472: 8462: 8457: 8455:Aortic rupture 8452: 8447: 8446: 8445: 8440: 8435: 8420: 8418: 8416:pseudoaneurysm 8403: 8402: 8399: 8398: 8396: 8395: 8390: 8385: 8380: 8375: 8369: 8367: 8363: 8362: 8360: 8359: 8354: 8348: 8346: 8340: 8339: 8337: 8336: 8335: 8334: 8329: 8327:Oxycholesterol 8324: 8319: 8314: 8309: 8299: 8293: 8292: 8291: 8290: 8285: 8280: 8275: 8270: 8259: 8257: 8248: 8242: 8241: 8239: 8238: 8233: 8232: 8231: 8220: 8218: 8209: 8194: 8193: 8185: 8184: 8177: 8170: 8162: 8153: 8152: 8149: 8148: 8139: 8128: 8117: 8105: 8104: 8102: 8098: 8097: 8094: 8093: 8082: 8071: 8060: 8041: 8017: 8012: 8011: 8009: 8008:Classification 8002: 8001: 7995: 7969: 7955: 7954:External links 7952: 7949: 7948: 7901: 7872:(4): 590–600. 7852: 7800: 7771:(5): 876–887. 7748: 7719:(2): 171–177. 7713:Nature Methods 7699: 7670:(4): 692–702. 7650: 7596: 7539: 7487: 7446: 7402: 7355: 7301: 7266: 7264: 7263: 7200: 7159: 7118: 7089:(7): 2921–31. 7069: 7020: 6977: 6939: 6904: 6857: 6822: 6781: 6740: 6713: 6695: 6654: 6607: 6575: 6565:. 15 July 2014 6550: 6503: 6468:(2): 213–237. 6448: 6421:(3): 251–265. 6401: 6381: 6357: 6298: 6239: 6214: 6163: 6142:(2): 317–327. 6122: 6071: 6050:(8): 924–936. 6030: 5981: 5952:(7): 782–790. 5932: 5903:(8): e005562. 5883: 5832: 5791: 5742: 5693: 5636: 5625:(2): 260–267. 5605: 5584:(10): 1731–7. 5564: 5545:(5): 431–434. 5526: 5519: 5497: 5461: 5434: 5385: 5342: 5313:(2): 130–138. 5293: 5249: 5228:(9): 1216–27. 5208: 5165: 5120: 5091:(4): 750–769. 5068: 5025: 5004:(7): 1282–92. 4984: 4949: 4928: 4907: 4866: 4833: 4818: 4796: 4755: 4734: 4715:(22): 1371–5. 4699: 4672:(6): 476–478. 4656: 4627:(9): 1166–72. 4606: 4576: 4549: 4524: 4479: 4459: 4432:(2): 157–163. 4416: 4370: 4352: 4317: 4273: 4232: 4197: 4172: 4123: 4101: 4052: 3998: 3939: 3890: 3855: 3814: 3785:(5): 1175–84. 3765: 3758: 3750:10.17226/10490 3730: 3695: 3654: 3633:(3): 392–403. 3613: 3594:(3): 333–342. 3578: 3549:(3): 298–314. 3529: 3517: 3476: 3439:(3): 270–279. 3419: 3370: 3323: 3280: 3231: 3180: 3131: 3095: 3083: 3053: 3011: 2981: 2940: 2921:(2): 201–205. 2902: 2883: 2874: 2823: 2799: 2792: 2772: 2765: 2745: 2686: 2637: 2612: 2601:. 22 June 2016 2586: 2555: 2536:(2): 203–214. 2520: 2455: 2444:. 22 June 2016 2424: 2390: 2366: 2359: 2336: 2325:. 22 June 2016 2301: 2290:. 22 June 2016 2270: 2259:. 22 June 2016 2241: 2216: 2205:. 22 June 2016 2187: 2176:. 22 June 2016 2151: 2150: 2148: 2145: 2142: 2141: 2123: 2122: 2120: 2117: 2108:myofibroblasts 2091: 2088: 2064:microorganisms 2055: 2054:Microorganisms 2052: 1995: 1992: 1900: 1897: 1826: 1823: 1821: 1818: 1813: 1810: 1736: 1733: 1692: 1689: 1669:anticoagulants 1664: 1661: 1628: 1625: 1604: 1601: 1564: 1561: 1542: 1539: 1535:blood pressure 1512:dairy products 1507: 1504: 1495: 1492: 1389:stress testing 1349: 1346: 1326: 1325: 1289: 1286: 1255: 1252: 1242: 1239: 1163: 1160: 1129: 1128: 1120: 1071: 1068: 1018:Rainer Liedtke 1005: 1002: 858: 855: 821:. The ensuing 819:cardiac muscle 794: 791: 727:of the second 721:Walter Willett 692: 689: 688: 687: 682: 680:Hypothyroidism 677: 675:Chronic stress 672: 667: 662: 657: 652: 647: 642: 637: 631: 625: 620: 613: 610: 609: 608: 605: 604:Family history 602: 597: 592: 584: 581: 580: 579: 574: 569: 564: 559: 554: 549: 544: 539: 534: 527: 524: 485: 482: 448:renal arteries 361: 358: 346:cause of death 212: 211: 208: 204: 203: 190: 184: 183: 177: 173: 172: 146: 140: 139: 136: 132: 131: 128: 124: 123: 106: 100: 99: 96: 90: 89: 80: 74: 73: 69: 68: 60: 59: 56: 52: 51: 43: 26: 9: 6: 4: 3: 2: 8981: 8970: 8969:Inflammations 8967: 8965: 8962: 8960: 8957: 8955: 8952: 8951: 8949: 8930: 8927: 8926: 8924: 8922: 8918: 8912: 8909: 8907: 8904: 8902: 8899: 8897: 8894: 8890: 8887: 8886: 8885: 8882: 8880: 8877: 8875: 8872: 8870: 8867: 8865: 8862: 8861: 8859: 8857: 8853: 8850: 8848: 8844: 8838: 8835: 8833: 8830: 8828: 8825: 8821: 8818: 8816: 8813: 8811: 8808: 8807: 8806: 8803: 8799: 8796: 8794: 8791: 8790: 8789: 8786: 8785: 8783: 8779: 8769: 8766: 8764: 8761: 8759: 8756: 8754: 8751: 8749: 8746: 8745: 8743: 8739: 8733: 8730: 8726: 8723: 8721: 8718: 8716: 8715:Caput medusae 8713: 8712: 8711: 8708: 8706: 8703: 8702: 8700: 8698: 8694: 8688: 8685: 8681: 8678: 8677: 8676: 8673: 8669: 8666: 8664: 8661: 8660: 8659: 8656: 8652: 8649: 8647: 8644: 8642: 8639: 8637: 8634: 8632: 8629: 8628: 8627: 8624: 8620: 8617: 8616: 8615: 8612: 8611: 8609: 8607: 8602: 8598: 8592: 8589: 8588: 8586: 8584: 8580: 8577: 8575: 8571: 8561: 8558: 8556: 8553: 8551: 8548: 8547: 8545: 8543: 8539: 8531: 8528: 8526: 8523: 8522: 8521: 8518: 8516: 8513: 8511: 8508: 8507: 8505: 8503: 8499: 8491: 8488: 8486: 8483: 8481: 8478: 8476: 8473: 8471: 8468: 8467: 8466: 8463: 8461: 8458: 8456: 8453: 8451: 8448: 8444: 8441: 8439: 8436: 8434: 8431: 8430: 8429: 8425: 8422: 8421: 8419: 8417: 8412: 8408: 8404: 8394: 8391: 8389: 8386: 8384: 8381: 8379: 8378:Degos disease 8376: 8374: 8371: 8370: 8368: 8364: 8358: 8355: 8353: 8350: 8349: 8347: 8345: 8341: 8333: 8330: 8328: 8325: 8323: 8320: 8318: 8315: 8313: 8310: 8308: 8305: 8304: 8303: 8300: 8298: 8295: 8294: 8289: 8286: 8284: 8281: 8279: 8276: 8274: 8271: 8269: 8266: 8265: 8264: 8261: 8260: 8258: 8256: 8252: 8249: 8247: 8243: 8237: 8234: 8230: 8227: 8226: 8225: 8222: 8221: 8219: 8217: 8213: 8210: 8208: 8203: 8199: 8195: 8190: 8183: 8178: 8176: 8171: 8169: 8164: 8163: 8160: 8147: 8143: 8140: 8138: 8134: 8133: 8129: 8127: 8123: 8122: 8118: 8116: 8112: 8111: 8107: 8106: 8103: 8099: 8092: 8088: 8087: 8083: 8081: 8077: 8076: 8072: 8070: 8066: 8065: 8061: 8059: 8055: 8051: 8050: 8046: 8042: 8040: 8036: 8032: 8028: 8027: 8023: 8019: 8018: 8015: 8010: 8006: 7999: 7996: 7994: 7990: 7984: 7980: 7979: 7975: 7970: 7967: 7962: 7958: 7957: 7944: 7940: 7936: 7932: 7928: 7924: 7920: 7916: 7912: 7905: 7897: 7893: 7888: 7883: 7879: 7875: 7871: 7867: 7863: 7856: 7848: 7844: 7839: 7834: 7830: 7826: 7822: 7818: 7814: 7807: 7805: 7796: 7792: 7787: 7782: 7778: 7774: 7770: 7766: 7762: 7755: 7753: 7744: 7740: 7735: 7730: 7726: 7722: 7718: 7714: 7710: 7703: 7695: 7691: 7686: 7681: 7677: 7673: 7669: 7665: 7661: 7654: 7646: 7642: 7637: 7632: 7628: 7624: 7620: 7616: 7612: 7605: 7603: 7601: 7592: 7588: 7583: 7578: 7574: 7570: 7566: 7562: 7558: 7554: 7550: 7543: 7535: 7531: 7526: 7521: 7517: 7513: 7509: 7505: 7501: 7494: 7492: 7483: 7479: 7474: 7469: 7465: 7461: 7457: 7450: 7442: 7438: 7433: 7428: 7425:(8): 927–32. 7424: 7420: 7416: 7409: 7407: 7398: 7394: 7390: 7386: 7382: 7378: 7374: 7370: 7366: 7359: 7351: 7347: 7342: 7337: 7332: 7327: 7323: 7319: 7315: 7308: 7306: 7297: 7293: 7289: 7285: 7281: 7277: 7270: 7260: 7256: 7250: 7249: 7246: 7242: 7237: 7232: 7228: 7224: 7220: 7216: 7212: 7204: 7196: 7192: 7187: 7182: 7179:(8): 1821–7. 7178: 7174: 7170: 7163: 7155: 7151: 7146: 7141: 7138:(6): 1057–8. 7137: 7133: 7129: 7122: 7114: 7110: 7105: 7100: 7096: 7092: 7088: 7084: 7080: 7073: 7065: 7061: 7056: 7051: 7047: 7043: 7039: 7035: 7031: 7024: 7016: 7012: 7008: 7004: 7000: 6996: 6992: 6988: 6981: 6973: 6969: 6965: 6961: 6958:(2): 314–23. 6957: 6953: 6946: 6944: 6935: 6931: 6927: 6923: 6919: 6915: 6908: 6900: 6896: 6892: 6888: 6884: 6880: 6876: 6872: 6868: 6861: 6853: 6849: 6845: 6841: 6837: 6833: 6826: 6818: 6814: 6809: 6804: 6800: 6796: 6792: 6785: 6777: 6773: 6768: 6763: 6759: 6755: 6751: 6744: 6736: 6732: 6728: 6724: 6717: 6709: 6705: 6704:"Atherogenic" 6699: 6691: 6687: 6682: 6677: 6673: 6669: 6665: 6658: 6650: 6646: 6642: 6638: 6634: 6630: 6626: 6622: 6618: 6611: 6598: 6594: 6590: 6586: 6579: 6564: 6560: 6554: 6546: 6542: 6538: 6534: 6530: 6526: 6522: 6518: 6514: 6507: 6499: 6495: 6491: 6487: 6483: 6479: 6475: 6471: 6467: 6463: 6459: 6452: 6444: 6440: 6436: 6432: 6428: 6424: 6420: 6416: 6412: 6405: 6399: 6395: 6391: 6385: 6371: 6367: 6361: 6353: 6349: 6344: 6339: 6334: 6329: 6325: 6321: 6317: 6313: 6309: 6302: 6294: 6290: 6285: 6280: 6275: 6270: 6266: 6262: 6258: 6254: 6250: 6243: 6228: 6224: 6218: 6210: 6206: 6201: 6196: 6191: 6186: 6182: 6178: 6174: 6167: 6159: 6155: 6150: 6145: 6141: 6137: 6133: 6126: 6118: 6114: 6109: 6104: 6099: 6094: 6090: 6086: 6082: 6075: 6067: 6063: 6058: 6053: 6049: 6045: 6041: 6034: 6026: 6022: 6017: 6012: 6008: 6004: 6000: 5996: 5992: 5985: 5977: 5973: 5968: 5963: 5959: 5955: 5951: 5947: 5943: 5936: 5928: 5924: 5919: 5914: 5910: 5906: 5902: 5898: 5894: 5887: 5879: 5875: 5870: 5865: 5860: 5855: 5851: 5847: 5843: 5836: 5828: 5824: 5819: 5814: 5810: 5806: 5802: 5795: 5787: 5783: 5778: 5773: 5769: 5765: 5761: 5757: 5753: 5746: 5738: 5734: 5729: 5724: 5720: 5716: 5713:(2): 307–13. 5712: 5708: 5704: 5697: 5689: 5685: 5680: 5675: 5671: 5667: 5663: 5659: 5655: 5651: 5647: 5640: 5632: 5628: 5624: 5620: 5616: 5609: 5601: 5597: 5592: 5587: 5583: 5579: 5575: 5568: 5560: 5556: 5552: 5548: 5544: 5540: 5533: 5531: 5522: 5516: 5512: 5508: 5501: 5493: 5489: 5485: 5481: 5477: 5473: 5465: 5457: 5453: 5449: 5445: 5438: 5430: 5426: 5421: 5416: 5412: 5408: 5404: 5400: 5396: 5389: 5381: 5377: 5373: 5369: 5365: 5361: 5357: 5353: 5346: 5338: 5334: 5329: 5324: 5320: 5316: 5312: 5308: 5304: 5297: 5289: 5285: 5281: 5277: 5273: 5269: 5265: 5261: 5253: 5245: 5241: 5236: 5231: 5227: 5223: 5219: 5212: 5204: 5200: 5195: 5190: 5186: 5182: 5181: 5176: 5169: 5161: 5157: 5152: 5147: 5143: 5139: 5135: 5131: 5124: 5116: 5112: 5107: 5102: 5098: 5094: 5090: 5086: 5082: 5075: 5073: 5064: 5060: 5056: 5052: 5048: 5044: 5041:(3): 188–95. 5040: 5036: 5029: 5021: 5017: 5012: 5007: 5003: 4999: 4995: 4988: 4980: 4976: 4972: 4968: 4965:(2): 115–26. 4964: 4960: 4953: 4944: 4939: 4932: 4923: 4918: 4911: 4903: 4899: 4895: 4891: 4886: 4881: 4877: 4870: 4854: 4850: 4846: 4840: 4838: 4829: 4825: 4821: 4815: 4810: 4809: 4800: 4792: 4788: 4783: 4778: 4774: 4770: 4766: 4759: 4744: 4738: 4730: 4726: 4722: 4718: 4714: 4710: 4703: 4695: 4691: 4687: 4683: 4679: 4675: 4671: 4667: 4660: 4652: 4648: 4643: 4638: 4634: 4630: 4626: 4622: 4618: 4610: 4602: 4598: 4594: 4590: 4583: 4581: 4572: 4568: 4564: 4560: 4553: 4538: 4534: 4528: 4520: 4516: 4511: 4506: 4502: 4498: 4494: 4490: 4483: 4475: 4474: 4469: 4463: 4455: 4451: 4447: 4443: 4439: 4435: 4431: 4427: 4420: 4413: 4409: 4405: 4401: 4397: 4393: 4389: 4385: 4381: 4374: 4366: 4362: 4356: 4348: 4344: 4340: 4336: 4332: 4328: 4321: 4313: 4309: 4305: 4301: 4297: 4293: 4289: 4285: 4277: 4269: 4265: 4260: 4255: 4251: 4247: 4243: 4236: 4228: 4224: 4220: 4216: 4212: 4208: 4201: 4186: 4182: 4176: 4168: 4164: 4159: 4154: 4150: 4146: 4142: 4138: 4134: 4127: 4119: 4115: 4111: 4105: 4097: 4093: 4089: 4085: 4080: 4075: 4071: 4067: 4063: 4056: 4049: 4045: 4041: 4036: 4031: 4026: 4021: 4017: 4013: 4012:PLOS Medicine 4009: 4002: 3994: 3990: 3985: 3980: 3975: 3970: 3966: 3962: 3958: 3954: 3950: 3943: 3935: 3931: 3926: 3921: 3917: 3913: 3909: 3905: 3901: 3894: 3886: 3882: 3878: 3874: 3870: 3866: 3859: 3851: 3847: 3842: 3837: 3834:(1): 136–40. 3833: 3829: 3825: 3818: 3810: 3806: 3801: 3796: 3792: 3788: 3784: 3780: 3776: 3769: 3761: 3755: 3751: 3747: 3743: 3742: 3734: 3726: 3722: 3718: 3714: 3710: 3706: 3699: 3691: 3687: 3682: 3677: 3674:(8): 821–30. 3673: 3669: 3665: 3658: 3650: 3646: 3641: 3636: 3632: 3628: 3624: 3617: 3609: 3605: 3601: 3597: 3593: 3589: 3582: 3574: 3570: 3565: 3560: 3556: 3552: 3548: 3544: 3540: 3533: 3527: 3521: 3513: 3509: 3504: 3499: 3496:(4): 461–91. 3495: 3491: 3487: 3480: 3472: 3468: 3464: 3460: 3455: 3450: 3446: 3442: 3438: 3434: 3430: 3423: 3415: 3411: 3406: 3401: 3397: 3393: 3390:(5): 339–50. 3389: 3385: 3381: 3374: 3366: 3360: 3358: 3356: 3354: 3352: 3350: 3348: 3346: 3344: 3342: 3340: 3338: 3336: 3334: 3332: 3330: 3328: 3319: 3315: 3311: 3307: 3303: 3299: 3295: 3291: 3284: 3276: 3272: 3267: 3262: 3258: 3254: 3251:(5): 551–61. 3250: 3246: 3242: 3235: 3227: 3223: 3218: 3213: 3208: 3203: 3199: 3195: 3191: 3184: 3176: 3172: 3167: 3162: 3158: 3154: 3150: 3146: 3142: 3135: 3126: 3122: 3118: 3114: 3110: 3106: 3099: 3086: 3080: 3076: 3072: 3068: 3064: 3057: 3049: 3045: 3041: 3037: 3033: 3029: 3022: 3015: 3000:on 2014-02-03 2999: 2995: 2988: 2986: 2977: 2973: 2968: 2963: 2960:(5): 859–69. 2959: 2955: 2951: 2944: 2936: 2932: 2928: 2924: 2920: 2916: 2909: 2907: 2898: 2892: 2890: 2888: 2878: 2870: 2866: 2862: 2858: 2854: 2850: 2846: 2842: 2838: 2834: 2827: 2813: 2809: 2803: 2795: 2789: 2785: 2784: 2776: 2768: 2762: 2758: 2757: 2749: 2741: 2737: 2733: 2729: 2724: 2723:10044/1/78967 2719: 2714: 2709: 2705: 2701: 2697: 2690: 2682: 2678: 2673: 2668: 2664: 2660: 2656: 2652: 2648: 2641: 2627: 2623: 2616: 2600: 2596: 2590: 2582: 2578: 2574: 2570: 2566: 2559: 2551: 2547: 2543: 2539: 2535: 2531: 2524: 2516: 2512: 2508: 2504: 2500: 2496: 2491: 2486: 2482: 2478: 2474: 2470: 2466: 2459: 2443: 2439: 2433: 2431: 2429: 2420: 2416: 2412: 2408: 2404: 2397: 2395: 2380: 2376: 2370: 2362: 2356: 2352: 2351: 2343: 2341: 2324: 2320: 2314: 2312: 2310: 2308: 2306: 2289: 2285: 2279: 2277: 2275: 2258: 2254: 2248: 2246: 2230: 2226: 2220: 2204: 2200: 2194: 2192: 2175: 2171: 2165: 2163: 2161: 2159: 2157: 2152: 2138: 2134: 2128: 2124: 2116: 2113: 2109: 2105: 2100: 2096: 2087: 2085: 2081: 2077: 2073: 2070:, changes in 2069: 2068:immune system 2065: 2061: 2051: 2049: 2045: 2041: 2037: 2033: 2032:RecQ helicase 2029: 2025: 2021: 2017: 2013: 2009: 2005: 2000: 1991: 1989: 1984: 1982: 1977: 1973: 1968: 1964: 1960: 1956: 1952: 1951:chromosome 22 1948: 1944: 1939: 1937: 1933: 1929: 1925: 1921: 1917: 1913: 1909: 1905: 1896: 1894: 1890: 1886: 1882: 1878: 1873: 1871: 1867: 1862: 1860: 1854: 1851: 1850: 1844: 1843:Apo-A1 Milano 1840: 1836: 1835:Apo-A1 Milano 1832: 1817: 1809: 1807: 1803: 1799: 1795: 1792: 1791:Ancient Greek 1788: 1784: 1780: 1776: 1772: 1770: 1764: 1761: 1757: 1754: 1750: 1746: 1742: 1732: 1729: 1727: 1722: 1720: 1715: 1713: 1709: 1705: 1701: 1696: 1688: 1686: 1682: 1678: 1674: 1670: 1660: 1658: 1654: 1650: 1646: 1642: 1638: 1634: 1624: 1621: 1617: 1614: 1610: 1600: 1596: 1592: 1590: 1586: 1582: 1578: 1574: 1570: 1560: 1559:obstruction. 1557: 1553: 1549: 1538: 1536: 1532: 1528: 1524: 1519: 1517: 1513: 1503: 1501: 1491: 1489: 1485: 1481: 1477: 1473: 1469: 1465: 1460: 1457: 1452: 1449: 1445: 1441: 1432: 1428: 1426: 1422: 1418: 1414: 1409: 1405: 1401: 1396: 1394: 1390: 1386: 1382: 1374: 1370: 1365: 1358: 1354: 1345: 1343: 1339: 1335: 1331: 1323: 1318: 1314: 1310: 1306: 1302: 1298: 1294: 1290: 1287: 1285:of the artery 1284: 1280: 1276: 1272: 1269: 1265: 1261: 1260: 1259: 1251: 1248: 1238: 1236: 1232: 1228: 1224: 1220: 1216: 1212: 1208: 1207:tissue factor 1204: 1199: 1195: 1191: 1188: 1183: 1181: 1177: 1168: 1159: 1157: 1153: 1149: 1144: 1140: 1138: 1134: 1126: 1121: 1118: 1114: 1110: 1109:proteoglycans 1106: 1102: 1097: 1093: 1092: 1091: 1085: 1081: 1076: 1067: 1065: 1061: 1055: 1053: 1049: 1045: 1044:smooth muscle 1041: 1037: 1032: 1030: 1026: 1021: 1019: 1014: 1010: 1009:Calcification 1001: 999: 995: 991: 987: 983: 982:smooth muscle 978: 976: 972: 968: 964: 960: 956: 952: 948: 943: 941: 940:free radicals 937: 933: 929: 925: 921: 917: 915: 914:Fatty streaks 911: 910:blood glucose 907: 903: 899: 895: 891: 883: 879: 875: 871: 867: 863: 854: 852: 848: 844: 840: 836: 832: 828: 827:tunica intima 824: 820: 816: 812: 808: 804: 800: 790: 787: 781: 779: 775: 774:Fred Kummerow 771: 766: 764: 763:hydroperoxide 761: 757: 753: 749: 744: 742: 738: 734: 730: 726: 722: 718: 714: 710: 706: 705:carbohydrates 702: 698: 686: 683: 681: 678: 676: 673: 671: 668: 666: 663: 661: 658: 656: 655:Air pollution 653: 651: 648: 646: 643: 641: 638: 636: 635:triglycerides 632: 630: 629:carbohydrates 626: 624: 623:Saturated fat 621: 619: 618:Thrombophilia 616: 615: 606: 603: 601: 598: 596: 593: 590: 587: 586: 583:Nonmodifiable 578: 575: 573: 570: 568: 565: 563: 560: 558: 555: 553: 550: 548: 545: 543: 540: 538: 535: 533: 530: 529: 523: 520: 515: 513: 509: 500: 495: 491: 481: 479: 475: 471: 466: 464: 460: 455: 453: 449: 445: 441: 438: 434: 432: 428: 424: 420: 416: 412: 408: 406: 402: 398: 397:Fatty streaks 395:of children. 394: 389: 387: 383: 379: 375: 371: 367: 357: 355: 351: 347: 342: 340: 336: 332: 328: 324: 320: 316: 311: 309: 305: 301: 297: 293: 289: 285: 281: 277: 273: 269: 265: 261: 257: 252: 250: 246: 242: 238: 234: 230: 226: 222: 218: 209: 205: 202: 198: 194: 191: 189: 185: 181: 178: 174: 170: 166: 162: 158: 154: 150: 147: 145: 141: 137: 133: 129: 125: 122: 118: 114: 110: 107: 105: 104:Complications 101: 97: 95: 91: 88: 84: 81: 79: 75: 70: 66: 61: 57: 53: 48: 40: 33: 19: 8856:Hypertension 8768:Venous ulcer 8674: 8657: 8625: 8613: 8583:Inflammation 8464: 8423: 8312:Hyperplastic 8273:Fatty streak 8262: 8216:Inflammation 8141: 8130: 8119: 8108: 8084: 8073: 8062: 8043: 8020: 7976: 7968:at Wikiquote 7918: 7914: 7904: 7869: 7865: 7855: 7820: 7816: 7768: 7764: 7716: 7712: 7702: 7667: 7663: 7653: 7618: 7614: 7556: 7552: 7542: 7507: 7503: 7466:(1): 42–50. 7463: 7459: 7449: 7422: 7418: 7372: 7368: 7358: 7321: 7317: 7279: 7275: 7269: 7258: 7218: 7214: 7203: 7176: 7172: 7162: 7135: 7131: 7121: 7086: 7082: 7072: 7040:(3): 241–7. 7037: 7033: 7023: 6993:(3): 220–5. 6990: 6986: 6980: 6955: 6951: 6917: 6913: 6907: 6874: 6870: 6860: 6835: 6831: 6825: 6801:(1): 18–28. 6798: 6794: 6784: 6757: 6753: 6743: 6726: 6716: 6707: 6698: 6671: 6668:Global Heart 6667: 6657: 6624: 6620: 6610: 6600:, retrieved 6588: 6578: 6567:. Retrieved 6562: 6553: 6520: 6516: 6506: 6465: 6461: 6451: 6418: 6414: 6404: 6389: 6384: 6373:. Retrieved 6369: 6360: 6315: 6311: 6301: 6256: 6252: 6242: 6231:. Retrieved 6217: 6180: 6176: 6166: 6139: 6135: 6125: 6091:(10): 2909. 6088: 6084: 6074: 6047: 6043: 6033: 5998: 5994: 5984: 5949: 5945: 5935: 5900: 5896: 5886: 5849: 5845: 5835: 5808: 5804: 5794: 5759: 5755: 5745: 5710: 5706: 5696: 5653: 5649: 5639: 5622: 5618: 5608: 5581: 5577: 5567: 5542: 5538: 5510: 5500: 5475: 5471: 5464: 5450:(7): 571–8. 5447: 5443: 5437: 5402: 5398: 5388: 5355: 5351: 5345: 5310: 5306: 5296: 5263: 5259: 5252: 5225: 5221: 5211: 5184: 5178: 5168: 5141: 5137: 5123: 5088: 5084: 5038: 5034: 5028: 5001: 4997: 4987: 4962: 4958: 4952: 4931: 4910: 4875: 4869: 4857:. Retrieved 4853:the original 4848: 4807: 4799: 4772: 4768: 4758: 4747:. Retrieved 4737: 4712: 4708: 4702: 4669: 4665: 4659: 4624: 4620: 4609: 4588: 4562: 4558: 4552: 4540:. Retrieved 4536: 4527: 4500: 4496: 4482: 4471: 4462: 4429: 4425: 4419: 4411: 4386:(5): 691–7. 4383: 4379: 4373: 4364: 4355: 4333:(1): 19–33. 4330: 4326: 4320: 4287: 4283: 4276: 4249: 4245: 4235: 4213:(4): 533–8. 4210: 4206: 4200: 4189:. Retrieved 4185:the original 4175: 4140: 4136: 4126: 4117: 4113: 4104: 4069: 4065: 4055: 4047: 4015: 4011: 4001: 3956: 3952: 3942: 3907: 3903: 3893: 3871:(2): 313–8. 3868: 3864: 3858: 3831: 3827: 3817: 3782: 3778: 3768: 3740: 3733: 3708: 3704: 3698: 3671: 3667: 3657: 3630: 3626: 3616: 3591: 3587: 3581: 3546: 3542: 3532: 3520: 3493: 3489: 3479: 3436: 3432: 3422: 3387: 3384:Arch Med Res 3383: 3373: 3293: 3289: 3283: 3248: 3244: 3234: 3197: 3193: 3183: 3148: 3144: 3134: 3108: 3104: 3098: 3088:, retrieved 3066: 3056: 3034:(1): 80–91. 3031: 3027: 3014: 3002:. Retrieved 2998:the original 2957: 2953: 2943: 2918: 2914: 2877: 2836: 2832: 2826: 2815:. 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