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Article Dans Une Revue Clinical Science Année : 2009

Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats

Cira Rt Di Gioia
  • Fonction : Auteur
Camila Bombardi
  • Fonction : Auteur
Carla Perego
  • Fonction : Auteur
Lucia Perego
  • Fonction : Auteur
Massimiliano Mancini
  • Fonction : Auteur
Martina Leopizzi
  • Fonction : Auteur
Barbara Corradi
  • Fonction : Auteur
Stefano Perlini
  • Fonction : Auteur
Gianpaolo Zerbini
  • Fonction : Auteur
Andrea Stella
  • Fonction : Auteur

Résumé

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a physiological tetrapeptide hydrolized by angiotensin converting enzyme. In experimental model of hypertension, Ac-SDKP has antifibrotic effects in the heart. The role of Ac-SDKP in diabetic cardiomyopathy is presently unknown. The aim of the study was to evaluate the effect of Ac-SDKP on cardiac systolic and diastolic function, interstitial and perivascular fibrosis in the heart of diabetic rats. Diabetes was induced in 55 Sprague Dawley rats by streptozotocin injection. Control rats (n=18) underwent only buffer injection. Out of 55 diabetic rats, 19 were chronically treated with insulin and 13 with the angiotensin converting enzyme inhibitor (ACEi), ramipril (3mg/kg/day). Two months after the onset of diabetes, Ac-SDKP (1mg/kg/day) was administered for 8 weeks to 8 control rats, 13 diabetic rats, 7 diabetic rats treated with ramipril and 9 insulin treated diabetic rats by osmotic minipumps. Diabetic rats had a significant increase in blood glucose level. Left ventricular interstitial and perivascular fibrosis and TGFb-1 protein levels were increased in diabetic rats, but not in insulin treated diabetic rats and in ramipril treated diabetic rats, as compared with control rats. Ac-SDKP administration significantly reduced left ventricular interstitial and perivascular fibrosis in diabetic rats and in diabetic rats treated with ramipril. This was accompanied by a significant reduction of active TGFb-1 and p-Smad2/3 protein levels in myocardial tissue of diabetic rats. Echocardiography showed that diabetes was associated with increased end systolic diameters, depressed global systolic function and diastolic dysfunction, as assessed by transmitral Doppler velocity profile. These changes were completely reverted by insulin or ramipril treatment. Ac-SDKP treatment partially restored diastolic function in diabetic rats. In diabetic rats, Ac-SDKP administration reduces left ventricular interstitial and perivascular fibrosis, active TGFb-1 and p-Smad2/3 levels, and improves diastolic function. Altogether these findings suggest that, by inhibiting TGFb/Smad pathway, Ac-SDKP protects against the development of diabetic cardiomyopathy.

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Dates et versions

hal-00531152 , version 1 (02-11-2010)

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Giovanna Castoldi, Cira Rt Di Gioia, Camila Bombardi, Carla Perego, Lucia Perego, et al.. Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats. Clinical Science, 2009, 118 (3), pp.211-220. ⟨10.1042/CS20090234⟩. ⟨hal-00531152⟩

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