Molecular Determinants of Atherosclerotic Plaque Vulnerability a

The devastating clinical consequences of atherosclerosis usually result from thrombotic complications of lesions. In the coronary circulation, a transient or subtotal thrombus may provoke unstable angina pectoris. A sustained, occlusive coronary thrombus often produces acute myocardial infarction. Data from recent anatomical and angiographic studies have provided considerable insight into the pathobiology of these clinical manifestations of coronary artery disease. We now recognize that many coronary thrombi result from a physical disruption of an atherosclerotic plaque. 1 ~ 3 In some cases, a superficial abrasion of the endothelial surface overlying an atherosclerotic plaque occurs. This type of desquamative injury uncovers constituents of the basement membrane including thrombogenic forms of collagen, inciting the formation of a clot. Another common type of disruption of atherosclerotic plaques results from an actual fracture or tear of the fibrous cap that typically overlies the lipid-rich core of advanced atherosclerotic plaques. Indeed, retrospective analyses of atherosclerotic plaques that have caused the demise of a patient frequently show such ruptures of the plaque's fibrous cap. Pathologic studies have revealed certain characteristics shared by plaques that have ruptured and provoked coronary thrombosis (TABLE 1 ) : ~ ~ Rupture-prone plaques tend to have thin fibrous caps, the structure that overlies the thrombogenic lipid-rich core of the lesion, separating it from the blood. Such plaques commonly contain large accumulations of lipid and many macrophage-derived foam cells. Regions of plaques that have ruptured characteristically contain foci of inflammation, as revealed by the presence of T lymphocytes and macrophages. Cells in the portions of these plaques often bear markers of inflammatory activation, such as the histocompatibility antigen HLA-DR. Interestingly, the region of the plaque at the site of rupture often has relatively few vascular smooth muscle cells. This finding contrasts with the widely held belief that this cell type predominates in the atherosclerotic intima.