Lipoprotein lipase (LPL) strongly links native and oxidized low density lipoprotein particles to decorin-coated collagen. Roles for both dimeric and monomeric forms of LPL.
Low density lipoprotein (LDL) and oxidized LDL are associated with collagen in the arterial intima, where the collagen is coated by the small proteoglycan decorin. When incubated in physiological ionic conditions, decorin-coated collagen bound only small amounts of native and oxidized LDL, the interaction being weak. When decorin-coated collagen was first allowed to bind lipoprotein lipase (LPL), binding of native and oxidized LDL increased dramatically (23- and 7-fold, respectively). This increase depended on strong interactions between LPL that was bound to the glycosaminoglycan chains of the collagen-bound decorin and native and oxidized LDL (kDa 12 and 5.9 nM, respectively). To distinguish between binding to monomeric (inactive) and dimeric (catalytically active) forms of LPL, affinity chromatography on heparin columns was conducted, which showed that native LDL bound to the monomeric LPL, whereas oxidized LDL, irrespective of the type of modification (Cu(2+), 2, 2'-azobis(2-amidinopropane)hydrochloride, hypochlorite, or soybean 15-lipoxygenase), bound preferably to dimeric LPL. However, catalytic activity of LPL was not required for binding to oxidized LDL. Finally, immunohistochemistry of atherosclerotic lesions of human coronary arteries revealed specific areas in which LDL, LPL, decorin, and collagen type I were present. The results suggest that LPL can retain LDL in atherosclerotic lesions along decorin-coated collagen fibers.
Pentikäinen
M O
MO
Wihuri Research Institute, 00140 Helsinki, Finland. markku.pentikainen@wri.fi
Oörni
K
K
Kovanen
P T
PT
D000327:Adsorption; D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002846:Chromatography, Affinity; D003094:Collagen / Q000378:metabolism*; D003331:Coronary Vessels / Q000033:anatomy & histology; D058575:Decorin; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D016326:Extracellular Matrix Proteins; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000378:metabolism* / Q000648:ultrastructure; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008892:Milk / Q000737:chemistry; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism*; D013997:Time Factors
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; C546878:DCN protein, human; D058575:Decorin; D004655:Emulsions; D016326:Extracellular Matrix Proteins; D005343:Fibrinolytic Agents; D008077:Lipoproteins, LDL; D011509:Proteoglycans; C099252:oxidized low density lipoprotein; D006493:Heparin; D003094:Collagen; D008071:Lipoprotein Lipase