Engineered heart tissue model of diabetic myocardium.

Myocardial infarction resulting in irreversible loss of cardiomyocytes (CMs) is a leading cause of heart failure. Previously, we reported an in vitro test-bed for screening cell integration between injected test cells and host CM using the engineered heart tissue as a recipient. The objective of this study is to expand our system to diabetic cardiomyopathy conditions. Patients with diabetes show dysfunction of CMs independent of myocardial infarction, indicating that diabetes directly affects CMs. However, the underlying mechanisms are not fully understood, and developing a diabetic CM test-bed could enable drug screening studies specific to the diabetic heart. Diabetic cardiac conditions were mimicked by cultivating neonatal rat CMs seeded onto collagen scaffolds in normal or high glucose with or without insulin. Our results show that high glucose conditions, which mimic diabetic hearts, display poor electrical properties. Gene expression profiles from diabetic, adult, and neonatal rat hearts as well as engineered heart tissues under different conditions were compared. The diabetic rat heart and high glucose conditions increased the ratio of myosin heavy-chain isoform β to α indicative of diseased states; thus, this model system captures some molecular aspects of diabetic cardiomyopathy. Moreover, thiazolidinedione diabetic drug treatment improved electrical excitabilities and exhibited anti-apoptotic effects.