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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1037.)
© 2004 American Heart Association, Inc.

Vascular Biology

Lipoprotein-Associated Phosphatidylethanol Increases the Plasma Concentration of Vascular Endothelial Growth Factor

Marja K. Liisanantti; Minna L. Hannuksela; Maria E. Rämet; Markku J. Savolainen

From the Department of Internal Medicine, University of Oulu, Oulu, Finland.

Correspondence to Prof Markku J. Savolainen, Department of Internal Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. E-mail markku.savolainen{at}oulu.fi

Objective— To study whether qualitative changes in high-density lipoprotein (HDL) phospholipids mediate part of the beneficial effects of alcohol on atherosclerosis, we investigated whether phosphatidylethanol (PEth) in HDL particles affects the secretion of vascular endothelial growth factor (VEGF) from endothelial cells.

Methods and Results— PEth increased the secretion of VEGF into the culture medium of EA.hy 926 endothelial cells. The mitogen-activated protein kinase (MAPK) phosphorylation increased by 3.3-fold and protein kinase C (PKC) by 2.2-fold by PEth-containing HDL. Moreover, we showed that intravenous injection of PEth incorporated into HDL particles increased plasma concentration of VEGF by 2.4-fold in rats in vivo. Similar effect was observed when the rats were injected with HDL particles isolated from alcohol drinkers.

Conclusions— HDL particles containing PEth affect endothelial cells by MAPK and PKC signaling. This may mediate the effects of ethanol on the arterial wall by increasing VEGF secretion from endothelial vascular cells. That may explain, at least in part, the beneficial effect of moderate alcohol consumption on atherosclerosis.

The present study shows that phosphatidylethanol in HDL particles can regulate vascular endothelial growth factor in endothelial cells by increasing the phosphorylation of mitogen-activated protein kinase and protein kinase C. This may contribute to the beneficial effects of alcohol on atherosclerosis.

Key Words: alcohol • endothelial cells • vascular endothelial growth factor • lipoproteins • phospholipids