沉默调节蛋白与烟酰胺腺嘌呤二核苷酸在代谢和心血管疾病的发生发展及治疗中的作用
Sirtuins and NAD in the Development and Treatment of Metabolic and Cardiovascular Diseases.
机构信息
From the Department of Genetics, Harvard Medical School, Boston, MA (A.E.K., D.A.S.).
Department of Pharmacology, The University of New South Wales, Sydney, Australia (D.A.S.).
出版信息
Circ Res. 2018 Sep 14;123(7):868-885. doi: 10.1161/CIRCRESAHA.118.312498.
The sirtuin family of nicotinamide adenine dinucleotide-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 injury, obesity, and cardiomyopathy, and SIRT3 is protective against dyslipidemia and ischemia-reperfusion injury. With increasing age, however, nicotinamide adenine dinucleotide levels and sirtuin activity steadily decrease, and the decline is further exacerbated by obesity and sedentary lifestyles. Activation of sirtuins or nicotinamide adenine dinucleotide 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 nicotinamide adenine dinucleotide levels are in progress and show promise in their ability to improve the health of cardiovascular and metabolic disease patients.
烟酰胺腺嘌呤二核苷酸依赖性去酰基酶（SIRT1-7）家族的去乙酰化酶被认为在很大程度上负责瘦饮食和运动对心血管代谢的益处，并且当被上调时可以延缓衰老的关键方面。例如，SIRT1 可防止血管内皮功能下降、代谢综合征、缺血再灌注损伤、肥胖和心肌病，而 SIRT3 可防止血脂异常和缺血再灌注损伤。然而，随着年龄的增长，烟酰胺腺嘌呤二核苷酸水平和 SIRT 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。在各种与年龄相关的心血管和代谢疾病模型中，激活 SIRT 或补充烟酰胺腺嘌呤二核苷酸可诱导血管生成、胰岛素敏感性和其他健康益处。正在进行人类临床试验，以测试激活 SIRT1 或提高烟酰胺腺嘌呤二核苷酸水平的药物，这些药物在改善心血管和代谢疾病患者的健康方面显示出希望。
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