Abstract 14164: Coenzyme Q10 Rescues Diastolic Dysfunction, Cardiomyocyte Hypertrophy and Cardiac Fibrosis in Female db/db Type 2 Diabetic Mice
Diabetic cardiomyopathy is characterised by early diastolic dysfunction and adverse LV remodeling (hypertrophy and fibrosis). We have previously shown that the progression of LV remodeling is similar in male and female diabetic db/db mice. Increased reactive oxygen species and/or reduced antioxidant defences have been implicated in the development of diabetic cardiomyopathy. The present study aimed to elucidate whether administering the endogenous antioxidant Coenzyme Q10 (CoQ) attenuates LV dysfunction and remodeling in a female mouse model of Type 2 diabetes. Non-diabetic db/+ and diabetic db/db 6wk old mice had solubilised CoQ (10mg/kg/day) added to their drinking water for 10wks. LV function was assessed by echocardiography and micromanometry; results were compared to untreated db/+ and db/db controls (n=11–13 mice/group). Untreated female db/db mice exhibited increases in body weight, lipid peroxidation, triglyceride and free fatty acid levels (see table). This was associated with diastolic dysfunction (on both LV end-diastolic pressure, LV EDP, and deceleration time), as well as increased cardiomyocyte size (H&E sections), cardiac fibrosis (collagen deposition, Sirius red) and systolic blood pressure (SBP). Systolic dysfunction was not evident. CoQ treatment significantly improved diastolic function in db/db mice, on deceleration time and LVEDP. Diabetes-induced cardiomyocyte hypertrophy and cardiac fibrosis were also blunted by CoQ. These actions were accompanied by enhanced glycemic control (on glycated hemoglobin, GHB) and modest lowering of SBP. In conclusion, these data strongly suggest that CoQ attenuates LV diastolic dysfunction and remodeling, which may be triggered by oxidative stress in the diabetic heart. Addition of CoQ to standard care may represent an improved treatment strategy for restoring cardiac function in diabetic patients. *p<0.05 vs untreated db/+, ^p<0.05 vs CoQ+db/+, #p<0.05 vs untreated db/db (two-way ANOVA)
- © 2010 by American Heart Association, Inc.