Diastolic dysfunction is more apparent in STZ-induced diabetic female mice, despite less pronounced hyperglycemia.
Chanchal ChandramouliMelissa E ReicheltClaire L CurlUpasna VarmaLaura A BienvenuParisa KoutsifeliAntonia J A RaaijmakersMiles J De BlasioCheng Xue QinAlicia J JenkinsRebecca H RitchieKimberley M MellorLea M D DelbridgePublished in: Scientific reports (2018)
Diabetic cardiomyopathy is a distinct pathology characterized by early emergence of diastolic dysfunction. Increased cardiovascular risk associated with diabetes is more marked for women, but an understanding of the role of diastolic dysfunction in female susceptibility to diabetic cardiomyopathy is lacking. To investigate the sex-specific relationship between systemic diabetic status and in vivo occurrence of diastolic dysfunction, diabetes was induced in male and female mice by streptozotocin (5x daily i.p. 55 mg/kg). Echocardiography was performed at 7 weeks post-diabetes induction, cardiac collagen content assessed by picrosirius red staining, and gene expression measured using qPCR. The extent of diabetes-associated hyperglycemia was more marked in males than females (males: 25.8 ± 1.2 vs 9.1 ± 0.4 mM; females: 13.5 ± 1.5 vs 8.4 ± 0.4 mM, p < 0.05) yet in vivo diastolic dysfunction was evident in female (E/E' 54% increase, p < 0.05) but not male diabetic mice. Cardiac structural abnormalities (left ventricular wall thinning, collagen deposition) were similar in male and female diabetic mice. Female-specific gene expression changes in glucose metabolic and autophagy-related genes were evident. This study demonstrates that STZ-induced diabetic female mice exhibit a heightened susceptibility to diastolic dysfunction, despite exhibiting a lower extent of hyperglycemia than male mice. These findings highlight the importance of early echocardiographic screening of asymptomatic prediabetic at-risk patients.
Keyphrases
- left ventricular
- diabetic rats
- oxidative stress
- type diabetes
- ejection fraction
- heart failure
- gene expression
- hypertrophic cardiomyopathy
- wound healing
- cardiac resynchronization therapy
- aortic stenosis
- acute myocardial infarction
- left atrial
- cardiovascular disease
- mitral valve
- blood pressure
- glycemic control
- dna methylation
- end stage renal disease
- high glucose
- cell death
- chronic kidney disease
- drug induced
- newly diagnosed
- atrial fibrillation
- endothelial cells
- weight loss
- blood glucose
- endoplasmic reticulum stress
- coronary artery disease
- computed tomography
- pregnancy outcomes
- stress induced
- prognostic factors