The Center of Cardiovascular Diseases, The First Hospital of Jilin University, Changchun 130021, China.
Pediatric Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Oxid Med Cell Longev. 2020 May 14;2020:6961348. doi: 10.1155/2020/6961348. eCollection 2020.
OVE26 mice are a widely used transgenic model of early-onset type 1 diabetes. These mice overexpress calmodulin in their pancreatic cells, develop severe diabetes within the first weeks of life, and progress to severe diabetic complications including diabetic nephropathy and diabetic cardiomyopathy (DCM). To date, diabetic nephropathy in OVE26 mice has been well explored, leaving the progression of DCM and the gender impact in this type 1 diabetes model still unrevealed. In our study, male and female OVE26 mice and age-matched nondiabetic FVB mice were examined at 4, 12, 24, and 36 weeks for their cardiac function, body weight, blood glucose, and heart weight/tibia length ratio. Further, histopathological examination and Western blot analysis for the key markers demonstrate that DCM appears at 24 weeks OVE26 mice, initiating with cardiac senescence, followed by fibrosis and then cardiac dysfunction. Mitochondrial respiration function analysis showed no indication of dysfunction in OVE26 mice at 24 weeks of age in both genders. In addition, no significant difference for the pathogenic progression was observed between OVE26 and FVB mice in both males and females. In conclusion, this study suggests cardiac senescence and fibrosis, which may be amended by sex differences, play key roles in the progression of DCM in OVE26 mice. The comprehensive characterization of diabetic cardiomyopathy progression and the sex difference impact in OVE26 mice provides a basis for future study on DCM using OVE26 mice.
OVE26 小鼠是一种广泛应用于早期 1 型糖尿病的转基因模型。这些小鼠在其胰腺β细胞中过度表达钙调蛋白，在生命的前几周内会发展为严重的糖尿病，并进展为严重的糖尿病并发症，包括糖尿病肾病和糖尿病心肌病（DCM）。迄今为止，OVE26 小鼠的糖尿病肾病已经得到了很好的研究，而 DCM 的进展和这种 1 型糖尿病模型中的性别影响仍未揭示。在我们的研究中，雄性和雌性 OVE26 小鼠以及年龄匹配的非糖尿病 FVB 小鼠在 4、12、24 和 36 周时检查其心脏功能、体重、血糖和心脏重量/胫骨长度比。此外，对关键标志物的组织病理学检查和 Western blot 分析表明，DCM 出现在 24 周龄的 OVE26 小鼠中，起始于心脏衰老，随后是纤维化，然后是心脏功能障碍。线粒体呼吸功能分析表明，在 24 周龄的雄性和雌性 OVE26 小鼠中，均未显示出功能障碍的迹象。此外，在雄性和雌性 OVE26 和 FVB 小鼠中，均未观察到致病进展存在显著差异。总之，本研究表明心脏衰老和纤维化可能通过性别差异在 OVE26 小鼠的 DCM 进展中起关键作用。对 OVE26 小鼠中 DCM 进展和性别差异影响的全面表征为使用 OVE26 小鼠进行 DCM 的未来研究提供了基础。
