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

Kim Connelly, Darren James Kelly, Yuan Zhang, David L Prior, Jennifer Martin, Alison Cox, K Thai, Michael P Feneley, J Tsoporis, K E White, Henry Krum, Richard E Gilbert

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60 Citations (Scopus)

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-beta (p
Original languageEnglish
Pages (from-to)280 - 291
Number of pages12
JournalCardiovascular Research
Volume76
Issue number2
Publication statusPublished - 2007

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