Abstract：
Nicotinamide adenine dinucleotide provides the critical redox pair, NAD+ and NADH, for cellular energy metabolism. In addition, NAD+ is the precursor for de novo NADP+ synthesis as well as the co-substrates for CD38, poly(ADP-ribose) polymerase and sirtuins, thus, playing a central role in the regulation of oxidative stress and cell signaling. Declines of the NAD+ level and altered NAD+/NADH redox states have been observed in cardiometabolic diseases of various etiologies. NAD based therapies have emerged as a promising strategy to treat cardiovascular disease. Strategies that reduce NAD+ consumption or promote NAD+ production have repleted intracellular NAD+ or normalized NAD+/NADH redox in preclinical studies. These interventions have shown cardioprotective effects in multiple models suggesting a great promise of the NAD+ elevating therapy. Mechanisms for the benefit of boosting NAD+ level, however, remain incompletely understood. Moreover, despite the robust pre-clinical studies there are still challenges to translate the therapy to clinic. Here, we review the most up to date literature on mechanisms underlying the NAD+ elevating interventions and discuss the progress of human studies. We also aim to provide a better understanding of how NAD metabolism is changed in failing hearts with a particular emphasis on types of strategies employed and methods to target these pathways. Finally, we conclude with a comprehensive assessment of the challenges in developing NAD-based therapies for heart diseases, and to provide a perspective on the future of the targeting strategies.
摘要：
烟酰胺腺嘌呤二核苷酸提供了关键的氧化还原对，NAD+和NADH,细胞能量代谢。此外,NAD是从头NADP合成的前体，也是CD38，聚（ADP-核糖）聚合酶和沉默调节蛋白的共底物，因此，在氧化应激和细胞信号调节中起着核心作用。在各种病因的心脏代谢疾病中已经观察到NAD水平的下降和NAD/NADH氧化还原状态的改变。基于NAD的疗法已成为治疗心血管疾病的有希望的策略。减少NAD+消耗或促进NAD+产生的策略在临床前研究中已经复制了细胞内NAD+或标准化的NAD+/NADH氧化还原。这些干预措施已在多种模型中显示出心脏保护作用，表明NAD升高疗法的前景广阔。提高NAD+水平的机制，然而,仍然不完全理解。此外，尽管进行了强有力的临床前研究,但将该疗法转化为临床仍存在挑战.这里,我们回顾了有关NAD+提升干预的机制的最新文献，并讨论了人类研究的进展。我们还旨在更好地了解NAD代谢在衰竭心脏中如何变化，特别强调所采用的策略类型和靶向这些途径的方法。最后,最后，我们对开发基于NAD的心脏病治疗方法的挑战进行了全面评估，并提供对目标战略未来的看法。
