title: Mild oxidation of lipoproteins increases their affinity for surfaces covered by heparan sulfate and lipoprotein lipase.
abstract: Lipoprotein lipase (LPL) is present in cells involved in development of atherosclerosis (endothelial cells, smooth muscle cells, and macrophages). A direct involvement of LPL in atherogenesis has been suggested. Previously we used the surface plasmon resonance technique to study the interaction of lipoproteins with surfaces covered by heparan sulfate proteoglycans (HSPG) and LPL [A. Lookene et al. (1997) Biochemistry 36, 5267-5275]. The binding was much increased by the presence of LPL. Here we demonstrate that mild oxidation of low-density-lipoprotein (LDL) and very-low-density lipoprotein (VLDL) 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 of the lipid part could explain the effects. LPL increased binding and uptake of the mildly oxidized (compared to nonoxidized) LDL by THP-I monocyte-derived macrophages. Our studies indicate that LPL has the highest affinity for mildly oxidized LDL and support its involvement in development of atherosclerosis.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeâ University, Umeâ, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Makoveichuk
authors.forename: A
authors.initials: A
authors.lastname: Lookene
authors.forename: G
authors.initials: G
authors.lastname: Olivecrona
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D002417:Cattle; D002460:Cell Line; D006497:Heparan Sulfate / Q000378:metabolism*; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D013499:Surface Properties
chemical_list: D006497:Heparan Sulfate; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; C099252:oxidized low density lipoprotein; C108132:oxidized very low density lipoprotein