Department of Nephrology, The First Hospital of Jilin University, Changchun, China.
Departments of Pediatrics, Radiation Oncology, Pharmacology and Toxicology, Pediatric Research Institute, The University of Louisville School of Medicine, Louisville, Kentucky, USA.
Curr Opin Nephrol Hypertens. 2021 Jan;30(1):108-114. doi: 10.1097/MNH.0000000000000660.
Sirtuins are a family of nicotinamide adenine dinucleotide+-dependent enzymes catalyzing target protein deacetylation to modulate cellular metabolism, response to oxidative stress and inflammation, senescence, autophagy and apoptosis. In this review, we provide an overview of recent studies regarding the alterations and roles of sirtuins in a variety of renal and cardiovascular diseases. We are also going to highlight activators and inhibitors of sirtuins in the prevention of these diseases. This will help us to understand how this field may change in the future.
Recent studies have elucidated how physical or diseased conditions alter the expressions and enzyme activity of sirtuins and expounded sexual differences in sirtuins functions. In addition, interventions by targeting sirtuins have been applied in preclinical and clinical studies to prevent or slow the development of related diseases.
The advantages of female sex in renal and cardiovascular diseases are partially due to the expression and function of sirtuins. Estrogen activates sirtuins and in turn sirtuins promote estrogen receptor signaling. In addition, the hypoglycemic agents, sodium-glucose cotransporter 2 inhibitors protect against diabetic nephropathy at least in part via activating SIRT-1. Although several compounds targeted sirtuins are promising drug candidates in a variety of renal and cardiovascular diseases, well designed large clinical trials are still required to identify their efficacy and safety.
烟酰胺腺嘌呤二核苷酸（NAD+）依赖性酶家族 Sirtuins 可催化靶蛋白去乙酰化，从而调节细胞代谢、氧化应激和炎症反应、衰老、自噬和细胞凋亡。本综述概述了近年来关于 Sirtuins 在多种肾脏和心血管疾病中的改变和作用的研究。我们还将重点介绍 Sirtuins 的激活剂和抑制剂在预防这些疾病中的作用。这将有助于我们了解该领域未来可能的变化。
最近的研究阐明了生理或疾病状态如何改变 Sirtuins 的表达和酶活性，并阐述了 Sirtuins 功能中的性别差异。此外，针对 Sirtuins 的干预措施已在临床前和临床试验中应用，以预防或减缓相关疾病的发展。
女性在肾脏和心血管疾病中具有优势，部分原因是 Sirtuins 的表达和功能。雌激素激活 Sirtuins，而 Sirtuins 又促进雌激素受体信号转导。此外，钠-葡萄糖共转运蛋白 2 抑制剂等降糖药物至少部分通过激活 SIRT-1 来预防糖尿病肾病。虽然几种靶向 Sirtuins 的化合物在多种肾脏和心血管疾病中是很有前途的候选药物，但仍需要精心设计的大型临床试验来确定它们的疗效和安全性。
