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

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

Epidemiology and Preventive Medicine Alfred Hospital

Research output: Contribution to journal › Article › Research › peer-review

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 language	English
Pages (from-to)	280 - 291
Number of pages	12
Journal	Cardiovascular Research
Volume	76
Issue number	2
Publication status	Published - 2007

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@article{eae77d08f9f94f3e9d033e93cebd269d,

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

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",

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

year = "2007",

language = "English",

volume = "76",

pages = "280 -- 291",

journal = "Cardiovascular Research",

issn = "0008-6363",

publisher = "Oxford University Press",

number = "2",

}

Functional, structural and molecular aspects of diastolic heart failure in the diabetic (mRen-2)27 rat. / Connelly, Kim; Kelly, Darren James; Zhang, Yuan; Prior, David L; Martin, Jennifer; Cox, Alison; Thai, K; Feneley, Michael P; Tsoporis, J; White, K E; Krum, Henry; Gilbert, Richard E.

In: Cardiovascular Research, Vol. 76, No. 2, 2007, p. 280 - 291.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Functional, structural and molecular aspects of diastolic heart failure in the diabetic (mRen-2)27 rat

AU - Connelly, Kim

AU - Kelly, Darren James

AU - Zhang, Yuan

AU - Prior, David L

AU - Martin, Jennifer

AU - Cox, Alison

AU - Thai, K

AU - Feneley, Michael P

AU - Tsoporis, J

AU - White, K E

AU - Krum, Henry

AU - Gilbert, Richard E

PY - 2007

Y1 - 2007

N2 - 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

AB - 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

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