Human Induced Pluripotent Stem Cell Modelling for Diabetic Cardiomyopathy and its Susceptibility to SARS-CoV2 myocardial damage

Abstract

For decades, it has been well known that patients with diabetes mellitus can develop ventricular dysfunction, even in the absence of coronary artery disease. The condition is commonly referred to as diabetic cardiomyopathy and is considered a cardiac muscle disorder due to the metabolic consequences of diabetes mellitus. It is characterized in the early stages by ventricular hypertrophy and diastolic dysfunction, and in later stages by systolic dysfunction that progresses to decompensated heart failure, resulting in morbidities and mortality. The pathogenesis of diabetic cardiomyopathy is complex and multifactorial. Mechanisms that include impaired calcium handling, up-regulated renin-angiotensin system, increased oxidative stress, altered substrate metabolism, and mitochondrial dysfunction have been implicated. In the COVID-19 pandemic, patients with diabetes mellitus infected with SARS-CoV-2 have a poorer prognosis including mortality. In this talk, I shall share our recent research findings using human induced pluripotent stem cell technology to identify potential mechanistic pathway related diabetic cardiomyopathy, and the direct therapeutic effects of SGLT inhibitors in diabetic cardiomyopathy, and the pathogenic link between SARS-CoV-2 infection and direct myocardial damage. Furthermore, our cardiac magnetic resonance imaging data has shown that patients with diabetes and impaired left ventricular ejection fraction, dapagliflozin alleviates cardiomyopathic changes.