HDL2 of heavy alcohol drinkers enhances cholesterol efflux from raw macrophages via phospholipid-rich HDL 2b particles

Alcohol Clin Exp Res. 2008 Jun;32(6):991-1000. doi: 10.1111/j.1530-0277.2008.00660.x.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcohol Drinking / blood*
  • Alcoholism / blood
  • Animals
  • Cell Line
  • Cholesterol / metabolism*
  • Cholesterol Ester Transfer Proteins / blood
  • Cholesterol, HDL / blood
  • High-Density Lipoproteins, Pre-beta / blood
  • Humans
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL2 / blood
  • Lipoproteins, HDL2 / metabolism*
  • Lipoproteins, HDL3 / blood
  • Macrophages / metabolism*
  • Male
  • Mice
  • Middle Aged
  • Phosphatidylcholine-Sterol O-Acyltransferase / blood
  • Phospholipid Transfer Proteins / blood

Substances

  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • High-Density Lipoproteins, Pre-beta
  • Lipoproteins, HDL
  • Lipoproteins, HDL2
  • Lipoproteins, HDL3
  • Phospholipid Transfer Proteins
  • Cholesterol
  • Phosphatidylcholine-Sterol O-Acyltransferase