内科学
内分泌学
载脂蛋白E
载脂蛋白B
脂蛋白
磷脂酰胆碱
心功能曲线
生物
胆固醇
磷脂
化学
医学
生物化学
疾病
心力衰竭
膜
作者
Laura K. Cole,Vernon W. Dolinsky,Jason R.B. Dyck,Dennis E. Vance
出处
期刊:Circulation Research
[Ovid Technologies (Wolters Kluwer)]
日期:2011-03-18
卷期号:108 (6): 686-694
被引量:45
标识
DOI:10.1161/circresaha.110.238691
摘要
Phosphatidylcholine (PC) is the predominant phospholipid component of circulating lipoproteins. The majority of PC is formed by the choline pathway. However, approximately one-third of hepatic PC can also be synthesized by phosphatidylethanolamine N-methyltransferase (PEMT). PEMT is required for normal secretion of very-low-density lipoproteins from the liver. We hypothesized that lack of PEMT would attenuate atherosclerosis and improve myocardial function.Investigate the contribution of PEMT to atherosclerotic lesion formation and cardiac function in mice that lack apolipoprotein E.Mice deficient in apolipoprotein E (Pemt(+/+)/Apoe(-/-)) and mice lacking both PEMT and apoE (Pemt(-/-)/Apoe(-/-)) were fed a chow diet for 1 year. The atherogenic lipoprotein profile of plasma of Apoe(-/-) mice was significantly improved by PEMT deficiency, with lower levels of triacylglycerol (45%) and cholesterol (≈25%) in the very-low-density lipoprotein and low-density/intermediate-density lipoprotein fractions, respectively (P < 0.05). Atherosclerotic lesion area was reduced by ≈30%, and aortic cholesteryl ester and cholesterol content were also reduced by ≈40% by PEMT deficiency (P < 0.05). By in vivo echocardiography, we detected a ≈50% improvement in systolic function in the Pemt(-/-)/Apoe(-/-) compared with Pemt(+/+)/Apoe(-/-) mice (P < 0.05). This was accompanied by a significant reduction in cardiac triacylglycerol (34%) in mice lacking PEMT.These results indicate that treatment strategies aimed at inhibition of PEMT might prevent the accumulation of cardiac triacylglycerol that predisposes individuals to compromised cardiac function.
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