title: N-methylnicotinamide protects against endothelial dysfunction and attenuates atherogenesis in apolipoprotein E-deficient mice.
abstract: Epidemiological studies have demonstrated that N-methylnicotinamide (MNA) may exert antithrombotic and anti-inflammatory effects on the endothelium. However, the exact role of MNA in endothelial function remains uncertain.
  
  
  
  Apolipoprotein E-deficient (apoE(-/-) ) mice fed with a high-fat, high-cholesterol diet (HCD) and human umbilical vein endothelial cells (HUVECs) were used to explore the role of MNA in endothelial function and its underlying mechanism. The endothelium-dependent vasorelaxation to acetylcholine in the aortas of low and high dose MNA-fed apoE(-/-) mice was improved by 24 and 36% (p < 0.05), respectively, compared with high-fat, HCD-fed control. MNA significantly increased nitric oxide/cyclic guanosinemonophosphate levels and decreased asymmetric dimethylarginine (ADMA) concentrations by induction of dimethylarginine dimethylaminohydrolase (DDAH)2 both in aorta and endothelial cells. Neither the activity nor the protein expression of DDAH1 was influenced upon MNA treatment. Then, DDAH2 depletion by RNA interference in HUVECs abolished the protective effect of MNA on endothelial function. Mechanically, this could be attributed to a direct modulation of the methylation level of DDAH2 gene promoter region by MNA.
  
  
  
  The present study reveals a novel mechanism through which MNA improves endothelial dysfunction and attenuates atherogenesis via the modulation of ADMA-DDAH axis.
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, P. R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, P. R. China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, P. R. China.
authors.forename: Hongen
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, P. R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Mu
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Xia
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006152:Cyclic GMP / Q000378:metabolism; D059305:Diet, High-Fat; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002791:Cholesterol, Dietary; D009536:Niacinamide; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase; D006152:Cyclic GMP; D000109:Acetylcholine; C008472:N-methylnicotinamide
keywords: Asymmetric dimethylarginine; Endothelial function; N-methylnicotinamide; Nitric Oxide; Oxidative stress