Diastolic dysfunction is more apparent in STZ-induced diabetic female mice, despite less pronounced hyperglycemia

Chandramouli, Chanchal, Reichelt, Melissa E., Curl, Claire L., Varma, Upasna, Bienvenu, Laura A., Koutsifeli, Parisa, Raaijmakers, Antonia J. A., De Blasio, Miles J., Qin, Cheng Xue, Jenkins, Alicia J., Ritchie, Rebecca H., Mellor, Kimberley M. and Delbridge, Lea M. D. (2018) Diastolic dysfunction is more apparent in STZ-induced diabetic female mice, despite less pronounced hyperglycemia. Scientific reports, 8 1: 2346. doi:10.1038/s41598-018-20703-8

Author Chandramouli, Chanchal
Reichelt, Melissa E.
Curl, Claire L.
Varma, Upasna
Bienvenu, Laura A.
Koutsifeli, Parisa
Raaijmakers, Antonia J. A.
De Blasio, Miles J.
Qin, Cheng Xue
Jenkins, Alicia J.
Ritchie, Rebecca H.
Mellor, Kimberley M.
Delbridge, Lea M. D.
Title Diastolic dysfunction is more apparent in STZ-induced diabetic female mice, despite less pronounced hyperglycemia
Journal name Scientific reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2018-02-05
Year available 2018
Sub-type Article (original research)
DOI 10.1038/s41598-018-20703-8
Open Access Status DOI
Volume 8
Issue 1
Start page 2346
Total pages 13
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract 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.
Keyword Cardiovascular-Disease
Mouse Model
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
Institute for Molecular Bioscience - Publications
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Created: Wed, 14 Feb 2018, 11:11:13 EST