HDL2 of Heavy Alcohol Drinkers Enhances Cholesterol Efflux From Raw Macrophages via Phospholipid‐Rich HDL2b Particles

Abstract

Alcohol consumption is associated with increased serum high density lipoprotein (HDL) cholesterol levels and a decreased risk for the development of atherosclerosis. However, the effects of heavy alcohol intake on reverse cholesterol transport, one of the key anti-atherogenic processes related to HDL, are poorly known. The ability of total HDL as well as HDL(2) and HDL(3) subclasses to promote cholesterol efflux from (3)H-cholesterol-labeled RAW 264.7 macrophages was studied among 6 heavy alcohol drinkers and 6 controls. Distribution of HDL subclasses was analyzed by 4 to 30% native gradient gels. Serum phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) activities were analyzed among several other biochemical measures. Cholesterol efflux to HDL(2) of heavy drinkers was 22% (p = 0.025) higher relative to controls. The increase in HDL(2) phospholipids, with a concomitant 2-fold (p = 0.055) increase in large HDL(2b) particles, was associated with enhanced cholesterol efflux to HDL(2). Interestingly, the cholesterol efflux to HDL(3) did not differ between the 2 study groups. These findings may be partially explained by a decreased CETP activity (-26%, p = 0.037) and an increased PLTP activity (39%, p = 0.045) in heavy drinkers. The increased cholesterol efflux potential of HDL(2) is most likely an anti-atherogenic feature linked to heavy alcohol consumption. The cholesterol efflux and HDL phospholipids also associated strongly within the whole study group (r(s) = 0.910, p <or= 0.01) suggesting a common pathway of enhanced cholesterol efflux via enlarged phospholipid-rich HDL particles.