| Abstract: | The endothelium provides a barrier between blood components and vessel wall cells. Changes in endothelial cell functions are pivotal to the pathogenesis of atherosclerosis. Endothelial cell expression of cell-surface vascular cell adhesion molecule-1 (VCAM-1) and vessel wall production of the monocyte chemoattractant protein-1 (MCP-1) coordinate the adhesion and migration of blood-borne monocytes into focal areas of vasculature during initiation and growth of an atherosclerotic lesion. The entry of monocytes into the vessel wall sets into motion a cascade of events that transforms these blood cells into lipid-laden foam cells, major components of an atherosclerotic lesion. The macrophage-foam cells modulate both endothelial and smooth muscle cell functions assuring growth of the lesion. As the lesion matures, the macrophages affect the stability of the plaque predisposing it to rupture. Therefore, accumulation of macrophages lays the groundwork for clinical sequelae such as plaque rapture, thrombosis and, eventually, myocardial infarction. Thus, endothelial cell dysfunction that results in monocyte recruitment profoundly influences atherosclerosis and provides the rationale for therapeutic intervention. This review discusses the cellular and molecular basis for monocyte accumulation in atherosclerosis and potential endothelial cell sites for pharmacological regulation. |
