Copper oxidation of in vitro dioleolylphosphatidylcholine-enriched high-density lipoproteins: Physicochemical features and cholesterol effluxing capacity

Susceptibility of Lipoproteins to oxidation is partly determined by their c ontent in endogenous antioxidants, but also by the polyunsaturated fatty ac ids (PUFA)/monounsaturated fatty acids (MUFA) ratio. The aim of our study w as to enrich human high-density lipoproteins (HDLs) with dioleoylphosphatid ylcholine (DOPC) in order to modify the PUFA/MUFA ratio while maintainig th e alpha-tocopherol/PUFA ratio constant and to appreciate the consequences o f this enrichment before and after copper-induced oxidation, The enrichment of HDLs with DOPC was obtained by incubation of these lipoproteins with DO PC liposomes and further reisolation of HDLs, The consequent 40% HDL enrich ment in MUFA was concomitant with a 35% loss in PUFA (MUFA/PUFA ratio = 1.4 3). The enrichment of HDLs with DOPC led to a 40% decrease in alpha-tocophe rol content, which kept a constant alpha-tocopherol/PUFA ratio. The DOPC-HD Ls exhibited a lower oxidizability by copper than the nonenriched HDLs (NE- HDLs), as shown by their twofold longer lag phase and the threefold lower p ropagation rate. Moreover, DOPC-HDLs led to a six- to sevenfold lower produ ction of hydroperoxide molecular species from phosphatidylcholine and chole steryl esters than NE-HDLs after 24 h copper oxidation, With regard to the cholesterol effluxing capacity, copper oxidation of HDLs led to a decrease of this property. However, our results clearly showed that DOPC enrichment of HDLs allowed us to keep a better effluxing capacity than in NE-HDLs afte r 24 h oxidation (22.3% vs 17.4%, respectively), Since apo A-I was degraded as well in DOPC-HDLs as in NE-HDLs, the better effluxing capacity of DOPC- HDLs could not come from a preserved integrity of apo A-I, It could be part ly related to the improved fluidity of oxidized DOPC-HDLs compared to oxidi zed NE-HDLs, as shown by electron spin resonance data (correlation-relaxati on time at 24 degrees C = 2.20 ns vs 3.00 ns after 24 h oxidation, in DOPC- HDLs and in NE-HDLs, respectively). Besides, it could also be hypothesized that the sevenfold lower content of phosphatidylcholine hydroperoxides in D OPC-HDLs than in NE-HDLs after 24 h copper oxidation could be involved in t he better ability of oxidized DOPC-HDLs to mobilize cellular cholesterol. ( C) 1999 Academic Press.