Proteoglycans, lipoproteins, and atherosclerosis

Abstract

The arterial wall proteoglycans play a crucial role in the pathogenesis of atherosclerosis as depicted schematically in Figure 7. Plasma components including lipoproteins cross the endothelium mainly by a non-specific bulk-phase vesicular transport. A selective interaction of apoB-containing lipoproteins occurs with proteoglycans of the subendothelial layer which results in extracellular retention and accumulation of lipoproteins. Such interaction alters the structural and charge characteristics of LDL particles. These altered LDL are taken up by monocyte-derived macrophages by scavenger receptor-mediated endocytosis, leading to cholesteryl ester accumulation and foam cell formation. Further, retention of LDL by proteoglycans in the extracellular matrix also increases the chances of oxidative modification of lipoproteins. All of these changes may be occurring at a marginal level as a normal adaptive process of the arterial wall. However, focal response to chronic hemodynamic stress, hyperlipidemia or other forms of injury may functionally alter the endothelium, and cause greater influx of lipoproteins and smooth muscle cell proliferation, resulting in increased synthesis of proteoglycans with altered characteristics. Enhanced binding of apo-B containing lipoproteins to proteoglycans under these conditions sets the stage for the development of athersclerosis.