Arterial wall proteoglycans--biological properties related to pathogenesis of atherosclerosis

The arterial wall is a complex organ system with respect to carbohydrate-protein macromolecules, particularly proteoglycans. Proteoglycans in the arterial wall display polydispersity and heterogeneity even in the same family. At least two major types are known: chondroitin sulphate-dermatan sulphate type and heparan sulphate type. These proteoglycans have varied biological properties, and some of these properties are implicated in the development of atherosclerosis. The chondroitin sulphate-dermatan sulphate proteoglycans are capable of forming complexes with serum low-density lipoproteins, a process conductive to lipid accumulation in the extracellular space of the arterial wall. Also, such reactions render low-density lipoprotein particles electronegative aggregates. These altered low-density lipoproteins are taken up by macrophages (and possibly by proliferative smooth muscle cells) through a high-affinity receptor pathway devoid of feedback regulation, which results in intracellular lipid accumulation and foam-cell formation, a hallmark of atherosclerosis. On the other hand, heparan sulphate proteoglycan located on the cell surface and internal elastic lamina is antithrombogenic, and facilitates binding of the lipid-clearing enzyme, lipoprotein lipase, to endothelium. Thus, chondroitin sulphate and heparan sulphate proteoglycans with divergent biological properties play a crucial role in the pathogenesis of atherosclerosis.