Sirtuins and NAD(+) in the Development and Treatment of Metabolic and Cardiovascular Diseases.
Sirtuins and NAD(+) in the Development and Treatment of Metabolic and Cardiovascular Diseases.
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DOI：
10.1161/circresaha.118.312498
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发表时间：
2018-09-14
影响因子：
20.1
通讯作者：
Sinclair DA
中科院分区：
文献类型：
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作者：
Kane AE;Sinclair DA
烟酰胺腺嘌呤二核苷酸（NAD+）依赖性脱酰基酶（SIRT 1 -7）的sirtuin家族被认为在很大程度上负责精益饮食和运动的心脏代谢益处，并且当上调时可以延迟衰老的关键方面。例如，SIRT 1可防止血管内皮功能下降、代谢综合征、缺血-再灌注（IR）损伤、肥胖和心肌病，而SIRT 3可防止血脂异常和IR损伤。然而，随着年龄的增长，NAD+水平和sirtuin活性稳步下降，肥胖和久坐不动的生活方式进一步加剧了这种下降。在广泛的年龄相关性心血管和代谢疾病模型中，sirtuins或NAD+补充的激活诱导血管生成、胰岛素敏感性和其他健康益处。测试激活SIRT 1或提高NAD+水平的药物的人体临床试验正在进行中，并显示出改善心血管和代谢疾病患者健康的能力。
The sirtuin family of nicotinamide adenine dinucleotide (NAD+)-dependent deacylases (SIRT1–7) are thought to be responsible, in large part, for the cardiometabolic benefits of lean diets and exercise and when upregulated can delay key aspects of aging. SIRT1, for example, protects against a decline in vascular endothelial function, metabolic syndrome, ischemia-reperfusion (IR) injury, obesity and cardiomyopathy, and SIRT3 is protective against dyslipidemia and IR injury. With increasing age, however, NAD+ levels and sirtuin activity steadily decrease and the decline is further exacerbated by obesity and sedentary lifestyles. Activation of sirtuins or NAD+ repletion induces angiogenesis, insulin sensitivity and other health benefits in a wide range of age-related cardiovascular and metabolic disease models. Human clinical trials testing agents that activate SIRT1 or boost NAD+ levels are in progress and show promise in their ability to improve the health of cardiovascular and metabolic disease patients.