title: 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.affiliation: Heart Failure Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Marissa A
authors.initials: MA
authors.lastname: Bowden
authors.affiliation: Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.|Department of Medicine, Monash University, Clayton, Victoria, Australia.
authors.forename: Greg H
authors.initials: GH
authors.lastname: Tesch
authors.affiliation: Heart Failure Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Julius
authors.affiliation: Heart Failure Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rosli
authors.affiliation: Heart Failure Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Love
authors.affiliation: Heart Failure Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.|Department of Medicine, Monash University, Clayton, Victoria, Australia.
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Ritchie
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008820:Mice, Obese / Q000378:metabolism*; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000378:metabolism; D020097:Natriuretic Peptide, Brain; D018384:Oxidative Stress / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1; D017382:Reactive Oxygen Species / Q000378:metabolism; D012737:Sex Factors; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D017395:Plasminogen Activator Inhibitor 1; D017382:Reactive Oxygen Species; C051321:SERPINE1 protein, human; D020097:Natriuretic Peptide, Brain