Changing concepts of atherogenesis

作者：Peter Libby · 发表于：Journal of Internal Medicine · 年份：2000 · DOI：10.1046/j.1365-2796.2000.00654.x · 被引用次数：628 · 研究领域：Atherosclerosis and Cardiovascular Diseases、Protease and Inhibitor Mechanisms、Cell Adhesion Molecules Research

This review discusses three stages in the life history of an atheroma: initiation, progression and complication. Recruitment of mononuclear leucocytes to the intima characterizes initiation of the atherosclerotic lesion. Specific adhesion molecules expressed on the surface of vascular endothelial cells mediate leucocyte adhesion: the selectins and members of the immunoglobulin superfamily such as vascular cell adhesion molecule-1 (VCAM-1). Once adherent, the leucocytes enter the artery wall directed by chemoattractant chemokines such as macrophage chemoattractant protein-1 (MCP-1). Modified lipoproteins contain oxidized phospholipids which can elicit expression of adhesion molecule and cytokines implicated in early atherogenesis. Progression of atheroma involves accumulation of smooth muscle cells which elaborate extracellular matrix macromolecules. These processes appear to result from an eventual net positive balance of growth stimulatory versus growth inhibitory stimuli, including proteins (cytokines and growth factors) and small molecules (e.g. prostanoids and nitric oxide). The clinically important complications of atheroma usually involve thrombosis. Arterial stenoses by themselves seldom cause acute unstable angina or acute myocardial infarction. Indeed, sizeable atheroma may remain silent for decades or produce only stable symptoms such as angina pectoris precipitated by increased demand. Recent research has furnished new insight into the molecular mechanisms that cau...