Transfer of phosphatidylethanol between lipoproteins.
BACKGROUND
Phosphatidylethanol (PEth) is an abnormal phospholipid formed only in the presence of ethanol. It has been recently shown that lipoprotein-associated PEth may mediate the effects of ethanol on endothelial cells, and this may explain, at least in part, the beneficial effect of ethanol on atherosclerosis. This study was performed to investigate the transfer of PEth between lipoproteins and the effects of PEth on cholesteryl ester transfer protein (CETP) activity in plasma.


METHODS
Lipoproteins were isolated from the plasma of healthy male volunteers (n = 16) and male alcoholics (n = 13). The transfer of cholesteryl esters and PEth was determined between labeled low-density lipoprotein (LDL) and unlabeled high-density lipoprotein particles in vitro. The electrophoretic mobility of PEth-modified LDL particles was determined by agarose gel electrophoresis.


RESULTS
PEth was transferred from PEth-modified LDL to high-density lipoprotein at an initial rate of 25.9 nmol/ml/hr. Monoclonal antibody (TP2) against the putative lipid-binding domain of CETP inhibited the transfer rate of PEth by approximately 64%, whereas the cholesteryl ester transfer was inhibited by 86%. This indicates that most of PEth was transferred by transfer proteins other than CETP.


CONCLUSIONS
The transfer of PEth between lipoproteins enables the redistribution of PEth from lipoprotein fractions with a slow turnover to those with a rapid clearance. Moreover, the PEth-induced change in the electrical charge of lipoproteins may affect the binding of lipoproteins to their receptors and binding proteins. This in turn may alter the metabolism of lipoproteins and lipid-mediated signaling pathways in the cells delineating the vascular wall.
Liisanantti
Marja K
MK
Department of Internal Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. marja.liisanantti@oulu.fi
Huhta
Kimmo
K
Savolainen
Markku J
MJ
D000328:Adult; D000437:Alcoholism / Q000097:blood; D000704:Analysis of Variance; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D020404:Glycerophospholipids / Q000097:blood*; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D020404:Glycerophospholipids; D006023:Glycoproteins; D008074:Lipoproteins; C051521:phosphatidylethanol