FOAM CELL CONVERSION OF MACROPHAGES ALTERS THE BIOSYNTHESIS OF HEPARAN-SULFATE

Heparan sulfate is thought to regulate the biological activities of se veral proteins implicated in the pathogenesis of atherosclerosis. Whil e the interactions of heparan sulfate with Lipoprotein lipase and vari ous growth factors have been actively studied, little is known of the cellular regulation of heparan sulfate biosynthesis in response to Lip id accumulation. We have investigated heparan sulfate biosynthesis dur ing conversion of murine J774 macrophages into lipid-laden foam cells. Such conversion is shown to accelerate the rate of glycosaminoglycan synthesis and the transport of newly synthesized proteoglycans into th e medium. Moreover, the structure of heparan sulfate is specifically a ltered due to an similar to 30% increase in the 6-O-sulfation of gluco samine residues within the N-sulfated heparan sulfate domains, whereas the sulfation of chondroitin sulfate remains unaffected. These result s suggest a selective effect of foam cell conversion on the biosynthes is of heparan sulfate. (C) 1998 Academic Press.