Proteoglycans in pathological conditions: atherosclerosis

Abstract

Proteoglycans accumulate within the innermost layer (intima) of blood vessels during atherosclerosis. This accumulation is marked in some forms of human atherosclerosis and is particularly prominent in vessels that have been experimentally injured and have healed by the process of reendothelialization. The two major cell types of the arterial wall, endothelium and smooth muscle, are the major sources of arterial proteoglycans, and cell cultures have demonstrated that these cells synthesize at least three families of proteoglycans similar to those present in human aorta. Each family differs with regard to molecular size, glycosaminoglycan and oligosaccharide content, and ability to aggregate in the presence of hyaluronic acid. Furthermore, each cell type possesses a distinct pattern of proteoglycan synthesis. Smooth muscle cells synthesize and secrete primarily chondroitin sulfate and dermatan sulfate-containing proteoglycans, whereas endothelial cells synthesize and secrete large amounts of heparan sulfate proteoglycan. Evidence is presented to indicate that the synthesis of proteoglycans is modulated as a function of growth and migratory state of the vascular cells.