Abstract P2166: Cardioprotective Effect Of Angiotensin Converting Enzyme 2 Activation In Hesc-derived Cardiomyocytes Under Diabetic Condition

Abstract

Diabetes mellitus (DM) is on the rise and has quickly become one of the most common and expensive chronic diseases in the world. DM and cardiovascular disease (CVD), the leading cause of morbidity and mortality in diabetic patients, have a close relationship. Diabetic cardiomyopathy (DCM) is a phenomenon comprising the deterioration in cardiac function and structure independent of coronary artery disease and other causes. However, there is still no specific and effective treatment of DCM. We investigated the cardioprotective effect of pharmacological activation of angiotensin converting enzyme 2 (ACE2) activator, diminazene aceturate (DIZE) in DCM in vitro model by using human embryonic stem cell (hESC)-derived cardiomyocytes under diabetic condition. In hESC-derived cardiomyocytes under diabetic condition, DIZE decerased the cardiomyocyte size and stabilized beating phenotypes. Furthermore, DIZE reduced the HF, cardiac hypertrophy, fibrosis, oxidative stress related gene expression, and ROS level and increased the mitochondrial function related gene expression and mitochondrial membrane potential. In transcriptome analysis, SERPINE1/PAI-1 and CCN2/CTGF are highly upregulated after DIZE treatment and might be candidate target genes of ACE2 activation. Collectively, ACE2 activation have a direct cardioprotective effect in hESC-derived cardiomyocytes under diabetic condition and can be a potential therapeutic target of DCM.