SIRT5‐Related Desuccinylation Modification Contributes to Quercetin‐Induced Protection against Heart Failure and High‐Glucose‐Prompted Cardiomyocytes Injured through Regulation of Mitochondrial Quality Surveillance

作者：Xing Chang, Tian Zhang, Junyan Wang, Yan Liu, Peizheng Yan, Qingyan Meng, Yongtian Yin, Shiyuan Wang · 发表于：Oxidative Medicine and Cellular Longevity · 年份：2021 · DOI：10.1155/2021/5876841 · 被引用次数：106 · 研究领域：Sirtuins and Resveratrol in Medicine、Mitochondrial Function and Pathology、Cardiovascular Function and Risk Factors

Myocardial fibrosis represents the primary pathological change associated with diabetic cardiomyopathy and heart failure, and it leads to decreased myocardial compliance with impaired cardiac diastolic and systolic function. Quercetin, an active ingredient in various medicinal plants, exerts therapeutic effects against cardiovascular diseases. Here, we investigate whether SIRT5‐ and IDH2‐related desuccinylation is involved in the underlying mechanism of myocardial fibrosis in heart failure while exploring related therapeutic drugs for mitochondrial quality surveillance. Mouse models of myocardial fibrosis and heart failure, established by transverse aortic constriction (TAC), were administered with quercetin (50 mg/kg) daily for 4 weeks. HL‐1 cells were pretreated with quercetin and treated with high glucose (30 mM) in vitro . Cardiac function, western blotting, quantitative PCR, enzyme‐linked immunosorbent assay, and immunofluorescence analysis were employed to analyze mitochondrial quality surveillance, oxidative stress, and inflammatory response in myocardial cells, whereas IDH2 succinylation levels were detected using immunoprecipitation. Myocardial fibrosis and heart failure incidence increased after TAC, with abnormal cardiac ejection function. Following high‐glucose treatment, HL‐1 cell activity was inhibited, causing excess production of reactive oxygen species and inhibition of mitochondrial respiratory complex I/III activity and mitochondrial antioxidant enzyme acti...