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作为与心源性猝死相关的心血管疾病新出现的治疗靶点的NAD代谢

NAD Metabolism as an Emerging Therapeutic Target for Cardiovascular Diseases Associated With Sudden Cardiac Death.

作者信息

Xu Weiyi, Li Le, Zhang Lilei

机构信息

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.

Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Front Physiol. 2020 Aug 13;11:901. doi: 10.3389/fphys.2020.00901. eCollection 2020.

Abstract

In addition to its central role in mediating oxidation reduction in fuel metabolism and bioenergetics, nicotinamide adenine dinucleotide (NAD) has emerged as a vital co-substrate for a number of proteins involved in diverse cellular processes, including sirtuins, poly(ADP-ribose) polymerases and cyclic ADP-ribose synthetases. The connection with aging and age-associated diseases has led to a new wave of research in the cardiovascular field. Here, we review the basics of NAD homeostasis, the molecular physiology and new advances in ischemic-reperfusion injury, heart failure, and arrhythmias, all of which are associated with increased risks for sudden cardiac death. Finally, we summarize the progress of NAD-boosting therapy in human cardiovascular diseases and the challenges for future studies.

摘要

除了在介导燃料代谢和生物能量学中的氧化还原反应方面发挥核心作用外,烟酰胺腺嘌呤二核苷酸(NAD)已成为多种参与不同细胞过程的蛋白质的重要辅助底物,这些细胞过程包括沉默调节蛋白、聚(ADP-核糖)聚合酶和环ADP-核糖合成酶。与衰老和年龄相关疾病的联系引发了心血管领域的新一轮研究热潮。在此,我们综述NAD稳态的基础知识、缺血再灌注损伤、心力衰竭和心律失常的分子生理学及新进展,所有这些都与心源性猝死风险增加相关。最后,我们总结了NAD增强疗法在人类心血管疾病中的进展以及未来研究面临的挑战。

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