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Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1349-55. doi: 10.1161/ATVBAHA.109.188672. Epub 2009 Jun 11.

Lack of phosphatidylethanolamine N-methyltransferase alters plasma VLDL phospholipids and attenuates atherosclerosis in mice.

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  • 1Department of Biochemistry, University of Alberta, Edmonton, Canada.

Abstract

OBJECTIVE:

Impaired hepatic phosphatidylcholine (PC) synthesis lowers plasma lipids. We, therefore, tested the hypothesis that lack of phosphatidylethanolamine N-methyltransferase (PEMT), a hepatic enzyme catalyzing PC biosynthesis, attenuates the development of atherosclerosis.

METHODS AND RESULTS:

Mice deficient in both PEMT and low-density lipoprotein receptors (Pemt(-/-)/Ldlr(-/-) mice) were fed a high-fat/high-cholesterol diet for 16 weeks. Atherosclerotic lesion area was approximately 80% lower (P<0.01) in Pemt(-/-)/Ldlr(-/-) mice than in Pemt(+/+)/Ldlr(-/-) mice, consistent with the atheroprotective plasma lipoprotein profile (ie, significant reduction in very low-density lipoprotein [VLDL]/intermediate-density lipoprotein/low-density lipoprotein-associated phospholipids [approximately 45%], triacylglycerols [approximately 65%], cholesterol [approximately 58%], and cholesteryl esters [approximately 68%]). Plasma apoB was decreased by 40% to 60%, whereas high-density lipoprotein levels were not altered. In addition, PEMT deficiency reduced plasma homocysteine by 34% to 52% in Pemt(-/-)/Ldlr(-/-) mice. The molar ratio of PC/phosphatidylethanolamine in nascent VLDLs produced by Pemt(-/-)/Ldlr(-/-) mice was lower than in VLDLs in Pemt(+/+)/Ldlr(-/-) mice. Furthermore, deletion of PEMT modestly reduced hepatic VLDL secretion in Ldlr(-/-) mice and altered the rate of VLDL clearance from plasma.

CONCLUSIONS:

This is the first report showing that inhibition of hepatic phospholipid biosynthesis attenuates atherosclerosis.

PMID:
19520976
[PubMed - indexed for MEDLINE]
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