The complement system in atherosclerosis

Abstract

Complement is a term referring to a collection of plasma proteins, specific cellular receptors and cell surface regulatory molecules. Activation of the complement system to completion results in the formation of C5b-9 terminal complexes. These complexes have been observed in human atherosclerotic lesions by immunohistochemistry. Although the structure(s) which activate complement in lesions have not been defined, cholesterol and oxysterols exhibit this property in vitro. Endothelial cell damage leads to complement activation and endothelial cells overlying atherosclerotic lesions have been observed to contain C3 and C5b-9 antigens. Cardiac myocytes stain for complement proteins (C3, C4 and C5b-9) following myocardial infarction. Infarct size and extent of inflammatory cell infiltrates are diminished by decomplementation prior to experimentally-induced myocardial ischemia. Following myocardial infarction and ulceration of atherosclerotic lesions in human patients there is an increase in circulating complement activation products and a decrease in the level of native C1 through C4 proteins. Thus, it appears that complement plays a role in atherogenesis and its sequelae. Little is known however, about the pathophysiological effects complement activation products exert on lesion development, for example through modulation of macrophage functions, or how complement activation is regulated in lesions. Implications for complement in atherogenesis are discussed.