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

Abstract

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 (β-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.

• Authors: Marissa A Bowden, Greg H Tesch, Tracey L Julius, Sarah Rosli, Jane E Love, Rebecca H Ritchie
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 23 Issue 6 Pg. 1166-77 (Jun 2015) ISSN: 1930-739X [Electronic] United States
• PMID: 25959739 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Obesity Society.

Chemical References

• Blood Glucose
• Plasminogen Activator Inhibitor 1
• Reactive Oxygen Species
• SERPINE1 protein, human
• Natriuretic Peptide, Brain

Topics

• Animals
• Blood Glucose (metabolism)
• Diabetes Mellitus, Type 2 (complications)
• Female
• Fibrosis
• Heart (physiopathology)
• Hypertrophy, Left Ventricular (physiopathology)
• Male
• Mice
• Mice, Obese (metabolism)
• Models, Animal
• Myocytes, Cardiac (metabolism)
• Natriuretic Peptide, Brain
• Oxidative Stress (physiology)
• Plasminogen Activator Inhibitor 1
• Reactive Oxygen Species (metabolism)
• Sex Factors
• Ventricular Remodeling (physiology)