Cholesterol efflux to high-density lipoproteins and apolipoprotein A-I phosphatidylcholine complexes is inhibited by ethanol: Role of apolipoprotein structure and cooperative interaction of phosphatidylcholine and cholesterol

There is a substantial body of evidence showing that moderate alcohol consu mption is associated with a reduced risk of cardiovascular morbidity and mo rtality. One of the factors thought to contribute to this reduction in risk is an increase in the level of high-density lipoproteins (HDL) correlated with alcohol consumption. However, HDL levels are elevated in heavy drinker s, but their risk of vascular disease is greater compared with that of mode rate drinkers. Ethanol at concentrations observed in heavy drinkers and alc oholics may directly act on HDL and apolipoproteins and in turn modify chol esterol efflux. In this paper, we show that ethanol significantly inhibited cholesterol efflux from fibroblasts to HDL and to apolipoprotein A-I (apoA -I) complexed with phosphatidylcholine (PC). Ethanol significantly inhibite d binding of PC to apoA-I, inhibited incorporation of cholesterol only when apoA-I contained PC, and did not alter incorporation of cholesterol into H DL. ApoA-I structure was altered by ethanol as monitored by steady-state fl uorescence polarization of tryptophan residues. The absence of ethanol effe cts on incorporation of cholesterol into HDL versus inhibition of cholester ol incorporation into the apoA-I-PC complex suggests that the effects of et hanol on cholesterol efflux mediated by HDL involve interaction with the ce ll surface and that efflux mediated by the apoA-I-PC complex is a combinati on of aqueous diffusion and contact with the eel surface. In addition, effe cts of ethanol on apoA-I suggest that pre-beta-HDL or lipid-free apoA-I may be more perturbed by ethanol than mature HDL, and such effects may be path ophysiological with respect to the process of reverse cholesterol transport in heavy drinkers and alcoholics.