Endothelial dysfunction in coronary heart disease.

Atherosclerosis is a chronic disease characterized by the focal accumulation of plaque (leukocytes, macrophages, smooth muscle cells, lipids, and extracellular matrix) in the vessel wall that ultimately leads to obstruction of the lumen through gradual progression, plaque rupture with intraluminal thrombosis, or both. The "vulnerable" plaque is smaller in size, richer in lipids, and more infiltrated with macrophages than the stable fibromuscular lesion. Therefore, lowering the lipid or macrophage pools stored in the plaque may stabilize the plaque and reduce the risk for plaque rupture. Indeed, cholesterol-lowering trials have yielded a significant reduction in acute cardiac events. Antithrombotic therapy may further prevent acute coronary syndromes by altering the consequences of plaque rupture. However, we need to address the earlier stages of atherosclerosis, namely, endothelial dysfunction. Current hypotheses concerning its pathogenesis focus on vascular endothelial injury, the oxidation of low-density lipoprotein and its effects on the endothelium, which set off a cascade or responses involving the complex interaction of growth factors and cytokines leading to increased oxidative stress, increased free radical formation, destruction of nitric oxide, endothelial dysfunction, increased platelet aggregation, thrombosis, inflammation, plaque formation, proteolysis, plaque fissure, and rupture.