Metabolism of oxidized phosphatidylcholines formed in oxidized low densitylipoprotein by lecithin-cholesterol acyltransferase

The possible involvement of lecithin-cholesterol acyltransferase (LCAT) in the metabolism of oxidized phosphatidylcholine (PC) in plasma was investiga ted. A variety of oxidized products are formed from PC following oxidation of low density lipoproteins (LDL), A significant increase in LDL oxidation levels in patients with familial LCAT deficiency (FLD) has been previously demonstrated by a sensitive sandwich ELISA for oxidized LDL using the monoc lonal antibody DLH3 which recognizes oxidized products of PC. In the presen t study, we found that LCAT produces various metabolites from oxidized PC a nd that oxidized PC molecules in LDL particles serve as substrates, When th e neutral lipid fraction was separated by TLC after the incubation of oxidi zed 1-palmitoyl-2- [1-C-14]linoleoyl PC with human plasma, a number of radi oactive bands were formed in addition to cholesteryl ester, These products were not formed from native 1-palmitoyl-2-[1-C-14]linoleoyl PC. Plasma from FLD patients also failed to form the additional products from oxidized PC. The addition of dithio-bis(nitrobenzoate) (DTNB), an LCAT inhibitor, or th e inactivation of LCAT activity by treating the plasma at 56 degrees C for 30 min abolished the generation of these products from oxidized PC. The act ivity was recovered in the high density lipoprotein (HDL) fraction but not in the LDL fraction separated from normal plasma. When 1-palmitoyl-2-[1-C-1 4] (9-oxononanoyl) PC and 1-stearoyl-2-[1-C-14] (5-oxovaleroyl)PC, PC oxida tion products that contain short chain aldehydes, were incubated with human plasma, radioactive products in the neutral lipid fraction were observed o n TLC, LDL containing oxidized PC was measured by sandwich ELISA using an a nti-apolipoprotein B antibody and DLH3. The reconstituted oxidized PC-LDL p articles were found to have lost their ability to bind DLH3 upon incubation with HDL, while the reactivity of the reconstituted oxidized PC-LDL remain ed unchanged in the presence of DTNB, These results suggest that LCAT is ca pable of metabolizing a variety of oxidized products of PC and preventing t he accumulation of oxidized PC in circulating LDL particles.