| Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats. | |
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MedLine Citation:
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PMID: 20310083 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a physiological tetrapeptide hydrolysed by ACE (angiotensin-converting enzyme). In experimental models of hypertension, Ac-SDKP has antifibrotic effects in the heart; however, the role of Ac-SDKP in diabetic cardiomyopathy is currently unknown. The aim of the present study was to evaluate the effect of Ac-SDKP on cardiac systolic and diastolic function, and 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 the 55 diabetic rats, 19 were chronically treated with insulin and 13 with the ACEI (ACE inhibitor) ramipril (3 mg x kg(-1 )of body weight x day(-1)). At 2 months after the onset of diabetes, Ac-SDKP (1 mg x kg(-1) of body weight x day(-1)) was administered by osmotic minipumps for 8 weeks to eight control rats, 13 diabetic rats, seven diabetic rats treated with ramipril and nine insulin-treated diabetic rats. Diabetic rats had a significant increase in blood glucose levels. Left ventricular interstitial and perivascular fibrosis, and TGF-beta1 (transforming growth factor-beta1) protein levels were increased in diabetic rats, but not in insulin-treated diabetic rats and ramipril-treated diabetic rats, 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 in active TGF-beta1 and phospho-Smad2/3 protein levels in myocardial tissue of diabetic rats. Echocardiography showed that diabetes was associated with increased end-systolic diameters, and depressed global systolic function and diastolic dysfunction, as assessed by transmitral Doppler velocity profile. These changes were completely reversed by insulin or ramipril treatment. Ac-SDKP treatment partially restored diastolic function in diabetic rats. In conclusion, Ac-SDKP administration in diabetic rats reduces left ventricular interstitial and perivascular fibrosis, active TGF-beta1 and phospho-Smad2/3levels, and improves diastolic function. Taken together, these findings suggest that, by inhibiting theTGF-beta/Smad pathway, Ac-SDKP protects against the development of diabetic cardiomyopathy |
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Authors:
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Giovanna Castoldi; Cira R T di Gioia; Camila Bombardi; Carla Perego; Lucia Perego; Massimiliano Mancini; Martina Leopizzi; Barbara Corradi; Stefano Perlini; Gianpaolo Zerbini; Andrea Stella |
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Publication Detail:
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Type: Journal Article Date: 2009-10-26 |
Journal Detail:
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Title: Clinical science (London, England : 1979) Volume: 118 ISSN: 1470-8736 ISO Abbreviation: Clin. Sci. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-03-22 Completed Date: 2010-03-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7905731 Medline TA: Clin Sci (Lond) Country: England |
Other Details:
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Languages: eng Pagination: 211-20 Citation Subset: IM |
Affiliation:
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Clinica Nefrologica, Az Ospedaliera San Gerardo, 20052 Monza, Italy. giovanna.castoldi@unimib.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin-Converting Enzyme Inhibitors
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administration & dosage Animals Cardiomyopathies / prevention & control Diabetes Complications / prevention & control* Diabetes Mellitus, Experimental / physiopathology* Fibrosis Heart Ventricles / drug effects, pathology* Hypoglycemic Agents / administration & dosage Insulin / administration & dosage Male Myocardium / pathology* Oligopeptides / administration & dosage, pharmacology* Ramipril / administration & dosage Rats Rats, Sprague-Dawley Smad Proteins / drug effects, metabolism Transforming Growth Factor beta1 / drug effects, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Hypoglycemic Agents; 0/Oligopeptides; 0/Smad Proteins; 0/Transforming Growth Factor beta1; 11061-68-0/Insulin; 120081-14-3/goralatide; 87333-19-5/Ramipril |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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