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. 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

Yang Zhao  1 , Brian Su, René L Jacobs, Brian Kennedy, Gordon A Francis, Emma Waddington, John T Brosnan, Jean E Vance, Dennis E Vance
Affiliations

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

Yang Zhao et al. Arterioscler Thromb Vasc Biol. 2009 Sep.

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.

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