LYSOLECITHIN-INDUCED ALTERATION OF SUBENDOTHELIAL HEPARAN-SULFATE PROTEOGLYCANS INCREASES MONOCYTE BINDING TO MATRIX

The cause and consequence of altered proteoglycans in atherosclerosis are poorly understood. To determine whether proteoglycans affect monoc yte binding, we studied the effects of heparin and proteoglycan degrad ing enzymes on THP-1 monocyte adhesion to subendothelial matrix (SEM). Monocyte binding increased about 2-fold after SEM was treated with he parinase. In addition, heparin decreased monocyte binding to fibronect in, a known SEM protein, by 60%. These data suggest that SEM heparan s ulfate inhibits monocyte binding to SEM proteins. We next examined whe ther lysolecithin, a constituent of modified lipoproteins, affects end othelial heparan sulfate proteoglycan (HSPG) production and monocyte b inding, Lysolecithin (10-200 mu M) decreased total (SO4)-S-35 in SEM ( 20-75%). 2-fold more monocytes bound to SEM from lysolecithin treated cells than to control SEM. Heparinase treatment did not further increa se monocyte binding 60 lysolecithin-treated SEM. HSPG degrading activi ty was found in medium from lysolecithin-treated but not control cells , (SO4)-S-35-labeled products obtained from labeled matrix treated wit h lysolecithin-conditioned medium were similar in size to those genera ted by heparinase. These data suggest that lysolecithin-treated endoth elial cells secrete a heparanase-like activity. We hypothesize that de creased vessel wall HSPG, as occurs in atherogenic conditions, allows increased monocyte retention within the vessel and is due to the actio ns of an endothelial heparanase.