Phosphatidylethanol mediates its effects on the vascular endothelial growth factor via HDL receptor in endothelial cells

Alcohol Clin Exp Res. 2009 Feb;33(2):283-8. doi: 10.1111/j.1530-0277.2008.00831.x. Epub 2008 Nov 19.


Background: Previous epidemiological studies have shown that light to moderate alcohol consumption has protective effects against coronary heart disease but the mechanisms of the beneficial effect of alcohol are not known. Ethanol may increase high density lipoprotein (HDL) cholesterol concentration, augment the reverse cholesterol transport, or regulate growth factors or adhesion molecules. To study whether qualitative changes in HDL phospholipids mediate part of the beneficial effects of alcohol on atherosclerosis by HDL receptor, we investigated whether phosphatidylethanol (PEth) in HDL particles affects the secretion of vascular endothelial growth factor (VEGF) by a human scavenger receptor CD36 and LIMPII analog-I (CLA-1)-mediated pathway.

Methods: Human EA.hy 926 endothelial cells were incubated in the presence of native HDL or PEth-HDL. VEGF concentration and CLA-1 protein expression were measured. Human CLA-1 receptor-mediated mechanisms in endothelial cells were studied using CLA-1 blocking antibody and protein kinase inhibitors.

Results: Phosphatidylethanol-containing HDL particles caused a 6-fold increase in the expression of CLA-1 in endothelial cells compared with the effect of native HDL. That emergent effect was mediated mainly through protein kinase C and p44/42 mitogen-activated protein kinase pathways. PEth increased the secretion of VEGF and that increase could be abolished by a CLA-1 blocking antibody.

Conclusions: High density lipoprotein particles containing PEth bind to CLA-1 receptor and thereby increase the secretion of VEGF from endothelial cells. Ethanol-induced protective effects against coronary heart disease may be explained, at least partly, by the effects of PEth-modified HDL particles on VEGF via CLA-1-mediated mechanisms in endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Carbazoles / pharmacology
  • Cell Line
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Flavonoids / pharmacology
  • Glycerophospholipids / antagonists & inhibitors
  • Glycerophospholipids / pharmacology*
  • Humans
  • Indoles
  • Lipoproteins / biosynthesis
  • Lipoproteins / genetics
  • Lipoproteins, HDL / drug effects*
  • Maleimides
  • Mitogen-Activated Protein Kinase 1 / biosynthesis
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology
  • Receptors, Lipoprotein / drug effects*
  • Vascular Endothelial Growth Factor A / metabolism*


  • 2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide
  • Carbazoles
  • Enzyme Inhibitors
  • Flavonoids
  • Glycerophospholipids
  • Indoles
  • Lipoproteins
  • Lipoproteins, HDL
  • Maleimides
  • Receptors, Lipoprotein
  • Vascular Endothelial Growth Factor A
  • high density lipoprotein receptors
  • phosphatidylethanol
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one