<i>N</i>‐methylnicotinamide protects against endothelial dysfunction and attenuates atherogenesis in apolipoprotein E‐deficient mice

Jiang, Nan; Wang, Min; Song, Jiayi; Liu, Yan; Chen, Hongen; Mu, Di; Xia, Min

doi:10.1002/mnfr.201501019

Cited by 15 publications

(13 citation statements)

References 34 publications

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“…Third, plasma NAM concentrations were not determined at the beginning of the experiment; however, genetically identical untreated ApoE-deficient mice had significantly lower plasma concentrations of NAM than NAM-treated mice. Fourth, me-NAM, a metabolic product of NAM [ 54 ], is also atheroprotective [ 76 , 77 ]. Thus, by increasing the plasma concentration of me-NAM, NAM administration might also contribute to preventing atherosclerosis development in vivo.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide Prevents Apolipoprotein B-Containing Lipoprotein Oxidation, Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice

et al. 2020

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The potential of nicotinamide (NAM) to prevent atherosclerosis has not yet been examined. This study investigated the effect of NAM supplementation on the development of atherosclerosis in a mouse model of the disease. The development of aortic atherosclerosis was significantly reduced (NAM low dose: 45%; NAM high dose: 55%) in NAM-treated, apolipoprotein (Apo)E-deficient mice challenged with a Western diet for 4 weeks. NAM administration significantly increased (1.8-fold) the plasma concentration of proatherogenic ApoB-containing lipoproteins in NAM high-dose (HD)-treated mice compared with untreated mice. However, isolated ApoB-containing lipoproteins from NAM HD mice were less prone to oxidation than those of untreated mice. This result was consistent with the decreased (1.5-fold) concentration of oxidized low-density lipoproteins in this group. Immunohistochemical staining of aortas from NAM-treated mice showed significantly increased levels of IL-10 (NAM low-dose (LD): 1.3-fold; NAM HD: 1.2-fold), concomitant with a significant decrease in the relative expression of TNFα (NAM LD: −44%; NAM HD: −57%). An improved anti-inflammatory pattern was reproduced in macrophages cultured in the presence of NAM. Thus, dietary NAM supplementation in ApoE-deficient mice prevented the development of atherosclerosis and improved protection against ApoB-containing lipoprotein oxidation and aortic inflammation.

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Section: Discussionmentioning

confidence: 99%

Nicotinamide Prevents Apolipoprotein B-Containing Lipoprotein Oxidation, Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice

et al. 2020

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“…This enzyme catalyses the methylation of nicotinamide (NA) with the use of S‐adenosyl‐methionine (SAM) as a methyl group donor, thus reduces an availability of NA as a substrate for NAD + synthesis and decreases SAM content. It was also suggested that the final product of NNMT activity that is methyl‐nicotinamide (MNA) may directly regulate inflammatory processes and influence eNOS activity in endothelial cells (Bar et al, 2017; Jiang et al, 2016). Therefore, a putative role of NNMT as an important regulatory enzyme involved in a proper endothelial functioning has been considered, and it was a reasonable justification of our study.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin and pravastatin stimulate nitric oxide and reactive oxygen species generation, affect mitochondrial network architecture and elevate nicotinamide N‐methyltransferase level in endothelial cells

Dymkowska

Wrzosek

Zabłocki

2020

J of Applied Toxicology

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Statins belong to the most often prescribed medications, which efficiently normalise hyperlipidaemia and prevent cardiovascular complications in obese and diabetic patients. However, beside expected therapeutic results based on the inhibition of 3‐hydroxyl‐3‐methylglutaryl‐CoA reductase, these drugs exert multiple side effects of poorly understood characteristic. In this study, side effects of pravastatin and atorvastatin on EA.hy926 endothelial cell line were investigated. It was found that both statins activate proinflammatory response, elevate nitric oxide and reactive oxygen species (ROS) generation and stimulate antioxidative response in these cells. Moreover, only slight stimulation of the mitochondrial biogenesis and significant changes in the mitochondrial network organisation have been noted. Although biochemical bases behind these effects are not clear, they may partially be explained as an elevation of AMP‐activated protein kinase (AMPK) activity and an increased activating phosphorylation of sirtuin 1 (Sirt1), which were observed in statins‐treated cells. In addition, both statins increased nicotinamide N‐methyltransferase (NNMT) protein level that may explain a reduced fraction of methylated histone H3. Interestingly, a substantial reduction of the total level of histone H3 in cells treated with pravastatin but not atorvastatin was also observed. These results indicate a potential additional biochemical target for statins related to reduced histone H3 methylation due to increased NNMT protein level. Thus, NNMT may directly modify gene activity.

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“…Furthermore, they showed that both of MNAM and perindopril activate ACE2/Ang-(1-7) and inhibit the ACE/Ang II axes and vasoprotective effects of MNAM were similar to perindopril (Bar et al, 2017). In addition, (Jiang et al, 2016) ADMA metabolizer-and thereby reduces ADMA levels and increases NO availability (Jiang et al, 2016).…”

Section: Figurementioning

confidence: 97%

“…Furthermore, they showed that both of MNAM and perindopril activate ACE2/Ang‐(1–7) and inhibit the ACE/Ang II axes and vasoprotective effects of MNAM were similar to perindopril (Bar et al, ). In addition, (Jiang et al, ) reported possible mechanism underlying the effects of MNAM on the regulation of ADMA levels. They indicated that MNAM probably controls methylation state of DDAM (dimethylarginine dimethylaminohydrolase)—a ADMA metabolizer—and thereby reduces ADMA levels and increases NO availability (Jiang et al, ).…”

Section: Mnam and Endothelial Functionmentioning

confidence: 99%

“…In addition, (Jiang et al, ) reported possible mechanism underlying the effects of MNAM on the regulation of ADMA levels. They indicated that MNAM probably controls methylation state of DDAM (dimethylarginine dimethylaminohydrolase)—a ADMA metabolizer—and thereby reduces ADMA levels and increases NO availability (Jiang et al, ).…”

Section: Mnam and Endothelial Functionmentioning

confidence: 99%

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N1‐methylnicotinamide (MNAM) as a guardian of cardiovascular system

Nejabati

Mihanfar

Pezeshkian

et al. 2018

Journal Cellular Physiology

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Atherosclerosis is identified as the formation of atherosclerotic plaques, which could initiate the formation of a blood clot in which its growth to coronary artery can lead to a heart attack. N-methyltransferase (NNMT) is an enzyme that converts the NAM (nicotinamide) to its methylated form, N1-methylnicotinamide (MNAM). Higher levels of MNAM have been reported in cases with coronary artery disease (CAD). Further, MNAM increases endothelial prostacyclin (PGI2) and nitric oxide (NO) and thereby causes vasorelaxation. The vasoprotective, anti-inflammatory and anti-thrombotic roles of MNAM have been well documented; however, the exact underlying mechanisms remain to be clarified. Due to potential role of MNAM in the formation of lipid droplets (LDs), it might exert its function in coordination with lipids, and their targets. In this study, we summarized the roles of MNAM in cardiovascular system and highlighted its possible mode of actions.

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N‐methylnicotinamide protects against endothelial dysfunction and attenuates atherogenesis in apolipoprotein E‐deficient mice

Abstract: The present study reveals a novel mechanism through which MNA improves endothelial dysfunction and attenuates atherogenesis via the modulation of ADMA-DDAH axis.

Cited by 15 publications

References 34 publications

Nicotinamide Prevents Apolipoprotein B-Containing Lipoprotein Oxidation, Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice

Nicotinamide Prevents Apolipoprotein B-Containing Lipoprotein Oxidation, Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice

Atorvastatin and pravastatin stimulate nitric oxide and reactive oxygen species generation, affect mitochondrial network architecture and elevate nicotinamide N‐methyltransferase level in endothelial cells

N1‐methylnicotinamide (MNAM) as a guardian of cardiovascular system

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