Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy

Abstract

The main cause of morbidity and mortality in diabetes mellitus (DM) is 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 diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and nonobese 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 affected left ventricular function and myocardial performance differently. T1DM displayed 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 in mice. T1DM and T2DM affected the whole cardiac transcriptome differently. In conclusion, the STZ-induced T1DM and T2DM mouse models showed significant differences in cardiac remodeling, function and the whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.

Ohwia caudata aqueous extract attenuates senescence in aging adipose-derived mesenchymal stem cells

“…Without such assessment, the observed beneficial effects in this study might solely stem from the protective activity of O. caudata against cytotoxicity rather than manifesting true anti-aging properties in doxorubicin-challenged hADSCs. Thirdly, investigating the delay or arrest in cell cycle progression and the expression of other genes associated with the aging process, such as β-galactosidase, p16INK4a, and p53 [ [53] , [54] , [55] , [56] ], would enhance the comprehensiveness of the results in the current study. Lastly, an in vivo study will be essential to substantiate the in vitro findings.…”

Roles of heat shock protein A12A in the development of diabetic cardiomyopathy

“…Interestingly, type 1 diabetic mice showed higher cardiomyocyte size (hypertrophy) compared with T2 diabetic mice. 31 Therefore, STZ-induced type 1 diabetes in mice is a proven and widely accepted model to study the pathogenesis of diabetes and its complications.…”

Senolytics rejuvenate the reparative activity of human cardiomyocytes and endothelial cells

“…Furthermore, the treatment need only be administered intermittently (e.g., monthly) as senolytics are administered in a hit-and-run approach [24] , which would further minimise the possibility of adverse side effects while increasing the compliance of the patients [25] . Senolytics could simultaneously target co-morbidities such as atherosclerosis [26] , diabetes [27,28] , and adverse cardiac remodelling [10] . Most importantly, they present the opportunity to prevent the disease before its manifestation by breaking down the mechanistic relationship between ageing and increased CVD risk.…”