Streptozotocin-induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy
The main cause of morbidity and mortality in diabetes mellitus (DM) are cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here we compared these two models for their effects on cardiac structure, function, and transcriptome. Different doses of STZ and different diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and non-obese sex and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR, and RNA-Seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM differently affect left ventricular function and myocardial performance. T1DM displays an exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis along with increased cardiac oxidative stress, CM DNA damage and senescence when compared to T2DM mice. T1DM and T2DM differently affect whole cardiac transcriptome. In conclusion, STZ-induced T1DM and T2DM mouse models show significant differences in cardiac remodeling, function and whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.