Cell dysfunction in atherosclerosis and the ischemic manifestations of coronary artery disease

Many of the cellular mechanisms and dysfunctions that underlie atherosclerotic plaque formation have been identified, including adverse interactions between atherogenic lipids and the arterial endothelium, loss of endothelium-dependent dilation, accumulation of inflammatory cells and mediators of inflammation in the intima of the arteries, and a decline in anticoagulant defenses. Several studies have shown that these mechanisms, which appear to be active throughout the pathogenesis and progression of atherosclerosis, are reversible within days, weeks, or months with effective lipid-lowering therapy. In addition, the findings of large-scale trials of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors suggest that the rapid improvement observed in trial participants is attributable to a reversal of endothelial and vascular wall dysfunctions rather than to a reduction in plaque size. The accumulated evidence indicates that improved endothelial function can benefit patients who have angina pectoris and/or are at risk for myocardial infarction. Current understanding of the cellular mechanisms of atherogenesis also suggests avenues of future research to refine treatment approaches and further improve outcomes for patients with coronary artery disease.