The vulnerable atherosclerotic plaque: pathogenesis and therapeutic approach.
Vascular inflammation not only plays a major role in the development of coronary atherosclerosis, but also contributes to the acute onset of thrombotic complications such as myocardial infarction, a leading cause of death in the United States [1]. Despite a gradual decrease in age-adjusted mortality attributable to acute myocardial infarction in the United States, cardiovascular disease is on the rise in many other countries. Macrophage accumulation and consequent production of proteolytic and thrombogenic molecules critically contribute to plaque disruption and thrombus formation, a frequent cause of fatal obstruction of the coronary arteries. A number of clinical studies suggest dyslipidemia as one of the major risk factors for coronary disease, and preclinical observations demonstrate that hypercholesterolemia promotes accumulation of oxidatively modified lowdensity lipoprotein (oxLDL) in the arterial wall, promoting endothelial cell (EC) dysfunction and, in turn, leukocyte invasion. Recent advances in vascular medicine have provided evidence that lipid-lowering therapy prevents acute coronary complications in patients, at least in part limiting inflammation in atheroma [2]. This article will review the role of dyslipidemia in the pathogenesis of vascular inflammation, and discuss the evidence for mechanisms by which lipid lowering prevents acute coronary events.