Sex Differences in Progression of Diabetic Cardiomyopathy in OVE26 Type 1 Diabetic Mice.

Abstract

OVE26 mice are a widely used transgenic model of early-onset type 1 diabetes. These mice overexpress calmodulin in their pancreatic β 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.