Insulin‐like growth factor <fc>II</fc> receptor alpha overexpression in heart aggravates hyperglycemia‐induced cardiac inflammation and myocardial necrosis: Fid-Bau Portal

Insulin‐like growth factor II receptor alpha overexpression in heart aggravates hyperglycemia‐induced cardiac inflammation and myocardial necrosis

Lai, Chin‐Hu / Van Thao, Dao / Tsai, Bruce Chi‐Kang / Hsieh, Dennis Jine‐Yuan / Chen, Michael Yu‐Chih / Kuo, Wei‐Wen / Kuo, Chia‐Hua / Lu, Shang‐Yeh / Liao, Shih‐Chieh / Lin, Kuan‐Ho / ... [mehr]

Abstract

Diabetes‐induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin‐like growth factor II receptor α (IGF‐IIRα) is a cardiac risk factor. In this study, we hypothesized IGF‐IIRα could also deteriorate diabetic heart injury. The results presented that both in vivo transgenic Sprague–Dawley rat model with specific IGF‐IIRα overexpression in the heart and in vitro myocardium H9c2 cells were used to investigate the negative function of IGF‐IIRα in diabetic hearts. The results showed that IGF‐IIRα overexpression aided hyperglycemia in creating more myocardial injury. Pro‐inflammatory factors, such as Tumor necrosis factor‐alpha, Interleukin‐6, Cyclooxygenase‐2, Inducible nitric oxide synthase, and Nuclear factor‐kappaB inflammatory cascade, are enhanced in the diabetic myocardium with cardiac‐specific IGF‐IIRα overexpression. Correspondingly, IGF‐IIRα overexpression in the diabetic myocardium also reduced the PI3K‐AKT survival axis and activated mitochondrial‐dependent apoptosis. Finally, both ejection fraction and fractional shortening were be significantly decrease in diabetic rats with cardiac‐specific IGF‐IIRα overexpression. Overall, all results provid clear evidence that IGF‐IIRα can enhance cardiac damage and is a harmful factor to the heart under high‐blood glucose conditions. However, the pathophysiology of IGF‐IIRα under different stresses and its downstream regulation in the heart still require further research.