Vascular Cell Proteoglycans: Evidence for Metabolic Modulation

Abstract

Proteoglycans accumulate in the intimal layer of blood vessels during the early stages of atherosclerosis and predispose the vessel wall to further complications of this disease. Arterial endothelial and smooth muscle cell cultures have been used to study the metabolism of vessel wall proteoglycans in an attempt to determine whether cellular events associated with the genesis of this disease, such as cellular proliferation, ageing, migration and interaction with components of the extracellular matrix, influence the metabolism of arterial proteoglycans. Proteoglycan analyses of vascular cells reveal that endothelial cells synthesize multiple species of heparan sulphate proteoglycan while smooth muscle cells synthesize little heparan sulphate proteoglycan but significant quantities of chondroitin and dermatan sulphate proteoglycan. Each family of proteoglycans synthesized by each cell type differs with regard to charge density, hydrodynamic size, glycosaminoglycan type and size, oligosaccharide content and ability to form high molecular weight aggregates. A monoclonal antibody has been generated against the chondroitin sulphate proteoglycan and used to immunolocalize this antigen to the interstitial matrix of normal and diseased blood vessels. Experiments are presented to indicate that proteoglycan metabolism is modulated when cultured arterial cells are stimulated to proliferate and migrate. Other factors shown to influence proteoglycan metabolism include the age of the cell and the nature of the substratum upon which the cells are grown. These culture systems provide useful models with which to study the factors involved in the regulation of proteoglycan synthesis by vascular cells.