What causes atherosclerosis?

Updated: Dec 30, 2019
  • Author: Elena R Ladich, MD; Chief Editor: Allen Patrick Burke, MD  more...
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The etiology of atherosclerosis is unknown, but there are multiple factors that contribute to atherosclerotic plaque progression. These include genetic and acquired factors. Processes involved in atherosclerosis include coagulation, inflammation, lipid metabolism, intimal injury, and smooth muscle cell proliferation (see the image below). Genes potentially involved in cardiovascular disease include APOA1, APOA5, APOB, APOC1, APOC2, APOE, CDKN1A, CXCL12, SCARB1, SMARCA4 and TERT. [2]

Atherosclerosis pathology. Spectrum of representat Atherosclerosis pathology. Spectrum of representative coronary lesion morphologies seen in our sudden death population, forming the basis for our modified American Heart Association (AHA) descriptive classification. The two nonprogressive lesions are intimal thickening and intimal xanthomas (foam cell collections known as fatty streaks, AHA type II). Pathologic intimal thickening (PIT) (AHA type III transitional lesions) marks the first of the progressive plaques, as they are the assumed precursors to more advanced fibroatheroma (FA). Thin-cap fibroatheromas (TCFAs) are considered precursors to plaque rupture. Essentially missing from the AHA consensus classification are alternative entities that give rise to coronary thrombosis, namely erosion and the calcified nodule. Erosions can occur on a substrate of PIT or FA, whereas calcified nodules depict eruptive fragments of calcium that protrude into the lumen, causing a thrombotic event. Lastly, healed plaque ruptures are lesions with generally smaller necrotic cores and focal areas of calcification where the surface generally shows areas of healing rich in proteoglycans. Multiple healed plaque ruptures are thought responsible for progressive luminal narrowing. Ca2+ = calcium; EL = extracellular lipid; FC = fibrous cap; NC = necrotic core; Th = luminal thrombus. (Reproduced with permission from Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. May 2000;20(5):1262-75.)

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