Mild oxidation of lipoproteins increases their affinity for surfaces covered by heparan sulfate and lipoprotein lipase

Lipoprotein lipase (LPL) is present in cells involved in development of ath erosclerosis (endothelial cells, smooth muscle cells, and macrophages). A d irect involvement of LPL in atherogenesis has been suggested. Previously we used the surface plasmon resonance technique to study the interaction of l ipoproteins with surfaces covered by heparan sulfate proteoglycans (HSPG) a nd LPL [A. Lookene et al. (1997) Biochemistry 36, 5267-5275], The binding w as much increased by the presence of LPL. Here we demonstrate that mild oxi dation of low-density-lipoprotein (LDL) and very-low-density lipoprotein (V LDL) in vitro increases their binding to surfaces covered by HSPG; and LPL, while extensive oxidation decreases it. Similar results were obtained with a lipid emulsion (Intralipid), indicating that oxidation-induced changes o f the lipid part could explain the effects. LPL increased binding and uptak e of the mildly oxidized (compared to nonoxidized) LDL by THP-I monocyte-de rived macrophages, Our studies indicate that LPL has the highest affinity f or mildly oxidized LDL and support its involvement in development of athero sclerosis, (C) 1998 Academic Press.