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Functional, structural and molecular aspects of diastolic heart failure in the diabetic (mRen-2)27 rat

Lookup NU author(s): Dr Kathryn White

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Abstract

Objective: Diabetic cardiomyopathy is an increasingly recognized cause of cardiac failure despite preserved left ventricular systolic function. Given the over-expression of angiotensin II in human diabetic cardiomyopathy, we hypothesized that combining hyperglycaemia with an enhanced tissue renin-angiotensin system would lead to the development of diastolic dysfunction with adverse remodeling in a rodent model. Methods: Homozygous (mRen-2)27 rats and non-transgenic Sprague Dawley (SD) rats were randomized to receive streptozotocin (diabetic) or vehicle (non-diabetic) and followed for 6 weeks. Prior to tissue collection, animals underwent pressure-volume loop acquisition. Results: Diabetic Ren-2 rats developed impairment of both active and passive phases of diastole, accompanied by reductions in SERCA-2a ATPase and phospholamban along with activation of the fetal gene program. Structural features of diabetic cardiomyopathy in the Ren-2 rat included interstitial fibrosis, cardiac myocyte hypertrophy and apoptosis in conjunction with increased activity of transforming growth factor-β (p < 0.01 compared with non-diabetic Ren-2 rats for all parameters). No significant functional or structural derangements were observed in non-transgenic, SD diabetic rats. Conclusion: These findings indicate that the combination of enhanced tissue renin-angiotensin system and hyperglycaemia lead to the development of diabetic cardiomyopathy. Fibrosis, and myocyte hypertrophy, a prominent feature of this model, may be a consequence of activation of the pro-sclerotic cytokine, transforming growth factor-beta, by the diabetic state. © 2007.

Publication metadata

Author(s): Connelly KA, Kelly DJ, Zhang Y, Prior DL, Martin J, Cox AJ, Thai K, Feneley MP, Tsoporis J, White KE, Krum H, Gilbert RE

Publication type: Article

Publication status: Published

Journal: Cardiovascular Research

Year: 2007

Volume: 76

Issue: 2

Pages: 280-291

ISSN (print): 0008-6363

ISSN (electronic): 1755-3245

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1016/j.cardiores.2007.06.022

DOI: 10.1016/j.cardiores.2007.06.022

PubMed id: 17716638

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