Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction.
Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction.
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DOI：
10.1016/j.jacbts.2022.06.012
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发表时间：
2022-12
影响因子：
9.7
通讯作者：
O'Brien, Kevin D.
中科院分区：
文献类型：
--
作者：
Wang, Dennis D.;Airhart, Sophia E.;Zhou, Bo;Shireman, Laura M.;Jiang, Siyi;Rodriguez, Carolina Melendez;Kirkpatrick, James N.;Shen, Danny D.;Tian, Rong;O'Brien, Kevin D.
在小鼠心肌病模型中，通过NR增加NAD+已显示出减缓心脏功能的恶化，并在一项小型非随机临床试验中表明具有抗炎作用。在本研究中，NR 2 g/d持续12周是安全的，耐受性良好，并可显著增加非卧床C期HFrEF患者的全血NAD+水平。全血NAD+对NR的反应与呼吸增加和PBMC中促炎细胞因子表达降低相关，这提供了增强NAD+作用于外周免疫细胞以减少全身炎症的证据。心力衰竭（HF）的线粒体功能障碍特征与细胞内烟酰胺腺嘌呤二核苷酸（NAD+）和NADH水平的变化相关。用NAD+前体烟酰胺核苷（NR）提高NAD+水平可能代表一种新的HF治疗方法。在这项由30名参与者组成的临床稳定HF伴射血分数降低患者试验中，NR剂量为1，000 mg，每日两次，似乎安全且耐受性良好，全血NAD+水平约为两倍。个体内NAD+增加与外周血单核细胞基础呼吸（R2 = 0.413，P = 0.003）和最大呼吸（R2 = 0.434，P = 0.002）增加以及NLRP 3表达降低（R2 = 0.330，P = 0.020）相关。（烟酰胺核苷治疗充血性心力衰竭; NCT 03423342）
Boosting NAD+ by NR has been shown to blunt worsening of cardiac function in murine cardiomyopathy models and suggested to have anti-inflammatory effects a small, nonrandomized clinical trial. In in this study, NR at 2 g/d over 12 weeks was safe, well tolerated, and significantly increased whole blood NAD+ levels in ambulatory stage C HFrEF patients. The whole blood NAD+ response to NR correlated with increased respiration and decreased proinflammatory cytokine expression in PBMCs, providing evidence that boosting NAD+ acts on peripheral immune cells to reduce systemic inflammation. The mitochondrial dysfunction characteristic of heart failure (HF) is associated with changes in intracellular nicotinamide adenine dinucleotide (NAD+) and NADH levels. Raising NAD+ levels with the NAD+ precursor, nicotinamide riboside (NR), may represent a novel HF treatment. In this 30-participant trial of patients with clinically stable HF with reduced ejection fraction, NR, at a dose of 1,000 mg twice daily, appeared to be safe and well tolerated, and approximately doubled whole blood NAD+ levels. Intraindividual NAD+ increases in response to NR correlated with increases in peripheral blood mononuclear cell basal (R2 = 0.413, P = 0.003) and maximal (R2 = 0.434, P = 0.002) respiration, and with decreased NLRP3 expression (R2 = 0.330, P = 0.020). (Nicotinamide Riboside in Systolic Heart Failure; NCT03423342)
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影响因子：
8
作者：
Martin, Angelical S.;Abraham, Dennis M.;Hirschey, Matthew D.
通讯作者：
Hirschey, Matthew D.
影响因子：
37.8
作者：
Diguet N;Trammell SAJ;Tannous C;Deloux R;Piquereau J;Mougenot N;Gouge A;Gressette M;Manoury B;Blanc J;Breton M;Decaux JF;Lavery GG;Baczkó I;Zoll J;Garnier A;Li Z;Brenner C;Mericskay M
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6
作者：
Seta, Y;Shan, K;Mann, D L
通讯作者：
Mann, D L
DOI：
10.1016/0735-1097(95)00589-7
发表时间：
1996-04-01
影响因子：
24
作者：
TorreAmione, G;Kapadia, S;Mann, DL
通讯作者：
Mann, DL
影响因子：
24
作者：
Fiuzat, Mona;Ezekowitz, Justin;O'Connor, Christopher M.
通讯作者：
O'Connor, Christopher M.