Why do plaques rupture?
Rupture of the plaque surface, often with thrombosis superimposed, occurs frequently during the evolution of coronary atherosclerotic lesions. It is probably the most important mechanism underlying the sudden, rapid plaque progression responsible for acute coronary syndromes. The risk of plaque rupture depends on plaque type (composition) rather than plaque size (volume), because only plaques rich in soft extracellular lipids are vulnerable (rupture-prone). Most ruptures are tiny, occurring at the periphery of the fibrous cap that covers the lipid-rich core--points where the cap is usually thinnest and most heavily infiltrated by macrophage foam cells. Compared with intact caps, ruptured ones usually have less tensile strength and are more extensible, containing less collagen and glycosaminoglycans, more extracellular lipid, fewer smooth muscle cells, and more macrophages. Progressive extracellular lipid accumulation (lipid core formation) and cap weakening (macrophage related?) predispose the plaque to rupture and determine the actual vulnerability, which may change with time. Luckily, the plaque components responsible for vulnerability (soft lipid and probably macrophages) are apparently most likely to regress with treatment. The dynamic interplay between the actual plaque vulnerability and external stresses ("triggers") probably determines the particular moment and point of rupture, if this occurs. Vulnerability probably plays a more important role in rupture than triggers, because exercise stress testing of patients with advanced coronary artery disease rarely triggers a rupture/thrombus-related acute heart attack. A prerequisite is the presence of a vulnerable plaque.
Falk
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University Institute of Forensic Medicine, Odense, Denmark.
D000375:Aging; D003324:Coronary Artery Disease / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control; D003329:Coronary Vasospasm / Q000150:complications; D015444:Exercise; D006339:Heart Rate; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D006973:Hypertension / Q000150:complications; D009200:Myocardial Contraction; D012307:Risk Factors; D012422:Rupture, Spontaneous; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects