N‐methylnicotinamide protects against endothelial dysfunction and attenuates atherogenesis in apolipoprotein E‐deficient mice. Issue 7 (4th May 2016)

• Record Type: Journal Article
• Authors: Jiang, Nan; Wang, Min; Song, Jiayi; Liu, Yan; Chen, Hongen; Mu, Di; Xia, Min
• Is Part Of: Molecular nutrition & food research. Volume 60:Issue 7(2016)
• Page Start: 1625
• Page End: 1636
• Publication Date: 2016-05-04
• Subjects: Asymmetric dimethylarginine -- Endothelial function -- N‐methylnicotinamide -- Nitric Oxide -- Oxidative stress; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201501019
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : MNA intervention improves endothelium‐dependent relaxation and inhibits the progression of atherosclerosis. MNA induces nitric oxide release and synthesis and preserves endothelial nitric oxide synthase activity through both reducing oxidative stress and inhibiting ADMA via promoting DDAH2 activity. Abstract : 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.