Earlier onset of diabesity-Induced adverse cardiac remodeling in female compared to male mice

OBJECTIVE: Emerging evidence suggests female type 2 diabetes (T2DM) patients may fare worse than males with respect to cardiovascular complications. Hence the impact of sex on relative progression of left ventricular (LV) remodeling in obese db/db mice was characterized. METHODS: The changes in parameters of LV hypertrophy (heart weight, pro-hypertrophic gene expression, cardiomyocyte size) and fibrosis (LV collagen deposition and oxidative stress), in parallel with body weight and blood glucose and lipid profiles, in male and female db/db T2DM mice, at 10, 14, and 18 weeks of age, were determined. RESULTS: Diabesity-induced cardiac remodeling was at least comparable in female (compared to male) mice. Females exhibited enhanced systemic oxidative stress and nonesterified fatty acid levels. Progression of LV pro-hypertrophic (beta-myosin heavy chain, B-type natriuretic peptide) and pro-oxidant gene expression (NADPH oxidase subunit Nox2, plasminogen activator inhibitor-1 PAI-I) was, however, exaggerated in females when expressed relative to 10-week-old db/db mice. Increased cardiomyocyte width was also evident earlier in db/db females than males. No other gender differences were observed. CONCLUSIONS: Progressive, age-dependent development of cardiac remodeling in db/db mice parallels impairments in glucose handling and oxidative stress. Certain aspects of the T2DM-induced LV remodeling response may have an earlier and/or exaggerated onset in diabetic females.