6533b85efe1ef96bd12bfafc

RESEARCH PRODUCT

The Participation of the Complement System in Atherosclerotic Vascular Disease

subject

description

Atherosclerosis is a vascular disease of large and medium-sized arteries wherein the tunica intima becomes thickened due to lipid accumulation, mostly cholesterol and its esters, smooth muscle cell proliferation, and increased deposition of connective tissue matrix. A major risk factor in the development of this disease is hypercholesterolemia arising from elevated levels of low density lipoproteins (LDL). The earliest recognizable lesion, which may be a precursor to the fibrofatty plaque, is the fatty streak. It is predominantly composed of monocyte-derived macrophage foam cells, i.e. cells ladened with intracellular lipid droplets. Hence, a fundamental aspect of atherogenesis is the insudation and accumulation of LDL-derived cholesterol and the attempt by monocyte/macrophages to clear it from the arterial wall. As lesion development progresses, the lipid component becomes surrounded by a fibrotic cap laid down by vascular smooth muscle cells. The proliferation of smooth muscle cells and induction of connective tissue synthesis is probably driven, at least in part, by the products released from resident macrophages. This chapter outlines the participation of the complement system in atherosclerosis. The ability of complement activation products to mediate proinflammatory functions of macrophages implicates this system in the pathogenesis of atherosclerotic lesion development.