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N ‐methylnicotinamide protects against endothelial dysfunction and attenuates atherogenesis in apolipoprotein E‐deficient mice
Author(s) -
Jiang Nan,
Wang Min,
Song Jiayi,
Liu Yan,
Chen Hongen,
Mu Di,
Xia Min
Publication year - 2016
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201501019
Subject(s) - endothelial dysfunction , asymmetric dimethylarginine , endocrinology , umbilical vein , medicine , endothelium , nitric oxide , apolipoprotein b , apolipoprotein e , chemistry , cholesterol , enos , endothelial stem cell , nitric oxide synthase , biochemistry , arginine , in vitro , disease , amino acid
Scope 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. Methods and results 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. Conclusions The present study reveals a novel mechanism through which MNA improves endothelial dysfunction and attenuates atherogenesis via the modulation of ADMA‐DDAH axis.