Document Detail


Upregulation of Bcl-2 proteins during the transition to pressure overload-induced heart failure.
MedLine Citation:
PMID:  17112608     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Cardiomyocyte apoptosis is implicated in the pathogenesis of heart failure and mitochondria play an important role in this mode of cell death. In this study, activity of the Bcl-2 family of mitochondrial apoptotic proteins and their regulator (p53) were assessed during the transition to heart failure. METHODS: Ten adult male sheep were banded with a variable aortic constriction device. This was progressively inflated to increase left ventricular (LV) afterload. The sheep were monitored echocardiographically, measuring LV Mass Index (LVMI), diastolic LV Internal Diameter (LVIDd) and Fractional Shortening (FS). Serial LV endomyocardial biopsies were obtained, to measure expression of p53 and Bcl-2 family proteins by Western blotting. RESULTS: Over the first 3-4 weeks, the sheep developed hypertrophy (LVMI 79.5+/-4.6 vs. 44.0+/-3.0 g/m2, p<0.01), followed by gradual LV dilatation (LVIDd 4.23+/-0.08 vs. 3.39+/-0.07 cm, p<0.01). Ventricular function remained stable until 7-8 weeks post banding, when there was significant deterioration (FS 18.3+/-2.4 vs. 46.9+/-2.6%, p<0.01), associated with clinical heart failure. Upregulation of the Bax/Bcl-2 ratio, associated with increased levels of p53, was demonstrated in each of the echocardiographically defined stages (LV hypertrophy, LV dilatation and LV failure). In parallel, significantly higher levels of anti-apoptotic protein (Bcl-xL) was associated with LV dilatation and failure. CONCLUSIONS: Upregulation of Bax/Bcl-2 ratio occurs during the transition to heart failure and in particular with the initial hypertrophic response. Increase in expression of the anti-apoptotic protein Bcl-xL suggests possible concomitant compensatory mechanisms being activated during the transition to heart failure.
Authors:
Narain Moorjani; Pedro Catarino; Danyah Trabzuni; Soad Saleh; Azad Moorji; Nduna Dzimiri; Futwan Al-Mohanna; Stephen Westaby; Manzoor Ahmad
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2006-11-16
Journal Detail:
Title:  International journal of cardiology     Volume:  116     ISSN:  1874-1754     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-16     Completed Date:  2007-04-09     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  27-33     Citation Subset:  IM    
Affiliation:
Department of Cardiothoracic Surgery, Oxford Heart Centre, John Radcliffe Hospital, Oxford OX3 9DY, United Kingdom. narain.moorjani@doctors.org.uk
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Heart Failure / complications,  metabolism*,  pathology
Heart Ventricles / ultrasonography
Male
Myocardium / pathology
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Reference Values
Sheep
Tumor Suppressor Protein p53 / metabolism
Ventricular Dysfunction, Left / etiology,  metabolism
Ventricular Pressure
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Suppressor Protein p53

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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