Cell surface heparan sulfate proteoglycans and lipoprotein metabolism

Cell surface heparan sulfate proteoglycans are involved in several aspects of the lipoprotein metabolism. Most of the biological activities of these p roteoglycans are mediated via interactions of their heparan sulfate moietie s with various protein ligands, including lipoproteins and lipases. The bin ding of lipoproteins to heparan sulfate is largely determined by their apop rotein composition, and apoproteins B and E display the highest affinity fo r heparan sulfate. Interactions of lipoproteins with heparan sulfate are im portant for the cellular uptake and turnover of lipoproteins, in part by en hancing the accessibility of lipoproteins to lipoprotein receptors and lipa ses. Apoprotein B may interact with receptors without involving heparan sul fate. Heparan sulfate has been further implicated in presentation and stabi lization of lipoprotein lipase and hepatic lipase on cell surfaces and in t he transport of lipoprotein lipase from extravascular cells to the luminal surface of the endothelia. In atherosclerosis, heparan sulfate is intimatel y involved in several events important to the pathophysiology of the diseas e. Heparan sulfate thus binds and regulates the activity of growth factors, cytokines, superoxide dismutase and antithrombin, which contribute to aber rant cell proliferation, migration and matrix production, scavenging of rea ctive oxygen radicals and thrombosis. In this review we discuss the various roles of heparan sulfate proteoglycans in vascular biology, with emphasis on interactions of heparan sulfate with lipoproteins and lipases and the mo lecular basis of such interactions.