Abstract:
Nicotinamide adenine dinucleotide (NAD+) is a central and pleiotropic metabolite involved in cellular energy metabolism, cell signaling, DNA repair, and protein modifications. Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Metabolic stress and aging directly affect the cardiovascular system. Compelling data suggest that NAD + levels decrease with age, obesity, and hypertension, which are all notable risk factors for CVD. In addition, the therapeutic elevation of NAD + levels reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances oxidative metabolism in vascular cells of humans and rodents with vascular disorders. In preclinical models, NAD + boosting can also expand the health span, prevent metabolic syndrome, and decrease blood pressure. Moreover, NAD + storage by genetic, pharmacological, or natural dietary NAD + -increasing strategies has recently been shown to be effective in improving the pathophysiology of cardiac and vascular health in different animal models, and human health. Here, we review and discuss NAD + -related mechanisms pivotal for vascular health and summarize recent experimental evidence in NAD + research directly related to vascular disease, including atherosclerosis, and coronary artery disease. Finally, we comparatively assess distinct NAD + precursors for their clinical efficacy and the efficiency of NAD + elevation in the treatment of major CVD. These findings may provide ideas for new therapeutic strategies to prevent and treat CVD in the clinic.
摘要:
烟酰胺腺嘌呤二核苷酸(NAD+)是参与细胞能量代谢的中枢多效代谢产物,细胞信号,DNA修复,和蛋白质修饰。心血管疾病(CVDs)是世界范围内的主要死亡原因。代谢应激和衰老直接影响心血管系统。令人信服的数据表明,NAD+水平随着年龄的增长而下降,肥胖,和高血压,这些都是CVD的显著危险因素。此外,NAD+水平的治疗性升高减少了慢性低度炎症,重新激活自噬和线粒体生物发生,并增强患有血管疾病的人类和啮齿动物的血管细胞中的氧化代谢。在临床前模型中,NAD+升压还可以扩大健康跨度,预防代谢综合征,降低血压.此外,NAD+遗传储存,药理学,或天然饮食NAD+增加策略最近已被证明在不同动物模型中有效改善心脏和血管健康的病理生理学,和人类健康。这里,我们回顾和讨论NAD+相关的血管健康的关键机制,并总结了NAD+研究中与血管疾病直接相关的最新实验证据,包括动脉粥样硬化,和冠状动脉疾病。最后,我们比较评估了不同的NAD+前体在治疗主要CVD中的临床疗效和NAD+升高的效率。这些发现可能为临床上预防和治疗CVD的新治疗策略提供思路。