Modelling Diabetic Cardiomyopathy: Using Human Stem Cell-Derived Cardiomyocytes to Complement Animal Models

Abstract

Diabetes is a global epidemic, with cardiovascular disease being the leading cause of death in diabetic patients. There is a pressing need for an in vitro model to aid understanding of the mechanisms driving diabetic heart disease, and to provide an accurate, reliable tool for drug testing. Human induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have potential as a disease modelling tool. There are several factors that drive molecular changes inside cardiomyocytes contributing to diabetic cardiomyopathy, including hyperglycaemia, lipotoxicity and hyperinsulinemia. Here we discuss these factors and how they can be seen in animal models and utilised in cell culture to mimic the diabetic heart. The use of human iPSC-CMs will allow for a greater understanding of disease pathogenesis and open up new avenues for drug testing.

Keywords: 3D cardiac organoids; animal models; cardiomyocytes; diabetes; diabetic cardiomyopathy; engineered heart tissue; environmental factors; heart disease; hiPSCs; in vitro disease modelling; maturation; metabolism.

Figure 1

Molecular mechanisms inducing diabetic cardiomyopathy. Elevated levels of plasma glucose and insulin in T2DM and increased lipolysis of fatty acids activates a number of adverse signaling pathways in cardiomyocytes. (Image created with BioRender.com).