RATIONALE: 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. OBJECTIVE: Investigate the contribution of PEMT to atherosclerotic lesion formation and cardiac function in mice that lack apolipoprotein E. METHODS AND RESULTS: 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. CONCLUSIONS: 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.
RATIONALE: 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. OBJECTIVE: Investigate the contribution of PEMT to atherosclerotic lesion formation and cardiac function in mice that lack apolipoprotein E. METHODS AND RESULTS: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. CONCLUSIONS: 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.
Authors: Maite Martínez-Uña; Marta Varela-Rey; Daniela Mestre; Larraitz Fernández-Ares; Olatz Fresnedo; David Fernandez-Ramos; Virginia Gutiérrez-de Juan; Idoia Martin-Guerrero; Africa García-Orad; Zigmund Luka; Conrad Wagner; Shelly C Lu; Carmelo García-Monzón; Richard H Finnell; Igor Aurrekoetxea; Xabier Buqué; M Luz Martínez-Chantar; José M Mato; Patricia Aspichueta Journal: J Hepatol Date: 2014-10-18 Impact factor: 25.083
Authors: Xia Gao; Jelske N van der Veen; Carlos Fernandez-Patron; Jean E Vance; Dennis E Vance; René L Jacobs Journal: J Lipid Res Date: 2015-06-25 Impact factor: 5.922