CCAAT/enhancer-binding protein β overexpression alleviates myocardial remodelling by regulating angiotensin-converting enzyme-2 expression in diabetes

Diabetic cardiomyopathy, a major cardiac complication, contributes to heart remodelling and heart failure. Our previous study discovered that CCAAT/enhancer-binding protein beta (C/EBP beta), a transcription factor that belongs to a family of basic leucine zipper transcription factors, interacts with the angiotensin-converting enzyme 2 (ACE2) promoter sequence in other disease models. Here, we aimed to determine the role of C/EBP beta in diabetes and whether ACE2 expression is regulated by C/EBP beta. A type 1 diabetic mouse model was generated by an intraperitoneal injection of streptozotocin. Diabetic mice were injected with a lentivirus expressing either C/EBP beta or sh-C/EBP beta or treated with valsartan after 12 weeks to observe the effects of C/EBP beta. In vitro, cardiac fibroblasts and cardiomyocytes were treated with high glucose (HG) to investigate the anti-fibrosis, anti-apoptosis and regulatory mechanisms of C/EBP beta. C/EBP beta expression was down-regulated in diabetic mice and HG-induced cardiac neonatal cells. C/EBP beta overexpression significantly attenuated collagen deposition and cardiomyocyte apoptosis by up-regulating ACE2 expression. The molecular mechanism involved the binding of C/EBP beta to the ACE2 promoter sequence. Although valsartan, a classic angiotensin receptor blocker, relieved diabetic complications, the up-regulation of ACE2 expression by C/EBP beta overexpression may exert greater beneficial effects on patients with diabetic cardiomyopathy.