SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart

• Published in: Cardiovascular diabetology Vol. 18; no. 1; pp. 15 - 13
• Main Authors: Li, Chenguang, Zhang, Jie, Xue, Mei, Li, Xiaoyu, Han, Fei, Liu, Xiangyang, Xu, Linxin, Lu, Yunhong, Cheng, Ying, Li, Ting, Yu, Xiaochen, Sun, Bei, Chen, Liming
• Format: Journal Article
• Language: English
• Published: England BioMed Central 02.02.2019; BMC
• Subjects: Animals; Antidiabetics; Antioxidant Response Elements; Antioxidants; Antioxidants - pharmacology; Apoptosis; Benzhydryl Compounds - pharmacology; Cardiomyopathy; Cardiovascular disease; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetic Cardiomyopathies - etiology; Diabetic Cardiomyopathies - metabolism; Diabetic Cardiomyopathies - physiopathology; Diabetic Cardiomyopathies - prevention & control; Disease Models, Animal; Echocardiography; Empagliflozin; Fibrosis; Glucose; Glucosides - pharmacology; Growth factors; Heart; Hyperglycemia; Immunohistochemistry; Insulin; Mice, Inbred C57BL; Myocardial fibrosis; Myocardium; Myocardium - metabolism; Myocardium - pathology; NF-E2-Related Factor 2 - metabolism; Original Investigation; Oxidants; Oxidative stress; Oxidative Stress - drug effects; Phosphorylation; Rodents; SGLT2; Signal Transduction - drug effects; Smad protein; Smad Proteins - metabolism; Sodium; Sodium-glucose cotransporter; Sodium-Glucose Transporter 2 - metabolism; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Structure-function relationships; Transforming growth factor; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b; Type 2 diabetes mellitus; Uric acid; Ventricular Function, Left - drug effects; Ventricular Remodeling - drug effects; Beijing China; China; Empagliflozin; Oxidative stress; Myocardial fibrosis; Type 2 diabetes mellitus; SGLT2
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-019-0816-2

Hyperglycaemia associated with myocardial oxidative stress and fibrosis is the main cause of diabetic cardiomyopathy. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor has recently been reported to improve glycaemic control in patients with type 2 diabetes in an insulin-independent manner. The aim of this study was to investigate the effect of empagliflozin on myocardium injury and the potential mechanism in type 2 diabetic KK-Ay mice. Thirty diabetic KK-Ay mice were administered empagliflozin (10 mg/kg/day) by oral gavage daily for 8 weeks. After 8 weeks, heart structure and function were evaluated by echocardiography. Oxidants and antioxidants were measured and cardiac fibrosis was analysed using immunohistochemistry, Masson's trichrome stain and Western blot. Results showed that empagliflozin improved diabetic myocardial structure and function, decreased myocardial oxidative stress and ameliorated myocardial fibrosis. Further study indicated that empagliflozin suppressed oxidative stress and fibrosis through inhibition of the transforming growth factor β/Smad pathway and activation of Nrf2/ARE signaling. Glycaemic control with empagliflozin significantly ameliorated myocardial oxidative stress injury and cardiac fibrosis in diabetic mice. Taken together, these results indicate that the empagliflozin is a promising agent for the prevention and treatment of diabetic cardiomyopathy.