Grant: Project Grant

Diabetes mellitus (DM) and obesity is the fifth leading cause of death worldwide and a major risk factor for various heart, vascular, and kidney diseases. Inhibition of the renin-angiotensin system (RAS) using angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) are key therapies for patients with diabetes. The ACE2/Ang 1-7 pathway provides a novel axis in the RAS which can be enhanced to provide therapeutic effects. The therapeutic relevance of our strategy is strengthened by the current clinical trials using rhACE2. ACE2 is also the receptor for the SARS-CoV-2 and our findings will have implications for patients with COVID-19. Relevance and Significance: We are studying strategies of enhancing Ang 1-7 action and/or ACE2 effects in male and female type 2 diabetic model with advanced diabetic complications and in diet-induced obese models. Despite the use of ACE inhibitors and angiotensin receptor blockers, diabetic cardiovascular complications remains major global health burdens for our patients and new therapies are needed. Our potential new therapies could have a dramatic beneficial impact on diabetic and obesity mediated micro and macrovascular complications. Importantly, we will also determine the sex-specific differences in these models and the response to increasing ACE2.