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

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    Author
    Chandramouli, C; Reichelt, ME; Curl, CL; Varma, U; Bienvenu, LA; Koutsifeli, P; Raaijmakers, AJA; De Blasio, MJ; Qin, CX; Jenkins, AJ; ...
    Date
    2018-02-05
    Source Title
    Scientific Reports
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Varma, Upasna; Curl, Claire; Mellor, Kimberley; Delbridge, Leanne; de Blasio, Miles; Bienvenu, Laura; Qin, Chengxue; Jenkins, Alicia; Ritchie, Rebecca
    Affiliation
    Physiology
    Pharmacology and Therapeutics
    Medicine and Radiology
    School of BioSciences
    Metadata
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    Document Type
    Journal Article
    Citations
    Chandramouli, C., Reichelt, M. E., Curl, C. L., Varma, U., Bienvenu, L. A., Koutsifeli, P., Raaijmakers, A. J. A., De Blasio, M. J., Qin, C. X., Jenkins, A. J., Ritchie, R. H., Mellor, K. M. & Delbridge, L. M. D. (2018). Diastolic dysfunction is more apparent in STZ-induced diabetic female mice, despite less pronounced hyperglycemia. SCIENTIFIC REPORTS, 8 (1), https://doi.org/10.1038/s41598-018-20703-8.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255886
    DOI
    10.1038/s41598-018-20703-8
    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.

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