[Current concepts of the pathogenesis of atherosclerosis]

Rupture of plaques followed by thrombosis and thrombo- or atheroembolism mark the clinical horizon of ischemic organ lesions in atherosclerosis. Initiation and development of lesions precede these often dramatic events by decades. Precursor lesions arise within the first, irreversible ones may develop from the second decade of life onwards. Two concurring or succeeding pathogenetic mechanisms dominate: 1. Discrete or functional endothelial injury (in conjunction with hemodynamic wall stresses and effects of endogenous or exogenous toxic factors such as hormones, immune- and other mediators, components of tobacco smoke, etc.) induces increased flow of low density lipoprotein (LDL) into arterial tissue. Immigrating monocytes capture LDL and accumulate its cholesterol as ester droplets becoming foam cells. Net flux and accumulation of cholesterol probably correlate with plasmatic LDL-cholesterol levels. 2. Endothelial denudation, also occurring under the influence of mechanical wall stresses and in particular over precursor lesions, incites platelet aggregation and clotting mechanisms. As a consequence, arterial smooth muscle proliferates in the sense of repair of injury, resulting in the formation of scar tissue. Lipid-rich lesions with scanty scars seem to be particularly prone to rupture and thus important complications. Plaque rupture is probably the most common complication leading to ischemic disease, whereby the extent of formation and organisation of thrombi might determine whether infarction or chronic ischemia is the outcome.