Document Detail


Augmentation of left ventricular mechanics by recirculation-mediated AAV2/1-SERCA2a gene delivery in experimental heart failure.
MedLine Citation:
PMID:  21289077     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Down-regulation of sarcoplasmic reticulum calcium ATPase (SERCA2a) is a key molecular abnormality in heart failure (HF), which is not currently addressed by specific pharmacotherapy. We sought to evaluate, in detail, the impact of augmented SERCA2a expression on left ventricular (LV) mechanics in a large animal model of HF. METHODS AND RESULTS: Heart failure was induced in adult sheep by rapid pacing (180 b.p.m.) for 1 month, followed by delivery of adeno-associated virus (AAV) 2/1-SERCA, using a percutaneous, recirculating system for gene delivery over a 10 min period. Left ventricular mechanics was investigated by echocardiography and conductance catheter measurements in sheep receiving AAV2/1-SERCA2a after a further 4 weeks of pacing in comparison with untreated HF controls. Left ventricular function was significantly improved in the AAV2/1-SERCA2a-treated group, despite continued pacing, as measured by fractional shortening (delta absolute FS, control -4.2 ± 1.5% vs. treatment 4.4 ± 1.5%; P < 0.01) and conductance catheterization (delta Ees, control -1.22 ± 0.60 vs. treatment 0.65 ± 0.51; P < 0.05). Western blots showed an increase in SERCA protein in AAV2/1-SERCA2a-treated animals, and an analysis of gene delivery showed no evidence of regional myocardial heterogeneity in the distribution of AAV2/1-SERCA. CONCLUSION: In a large animal model, AAV2/1-mediated SERCA2a gene delivery using percutaneous, recirculating cardiac delivery leads to improved LV function.
Authors:
Justin A Mariani; Anka Smolic; Arthur Preovolos; Melissa J Byrne; John M Power; David M Kaye
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-2
Journal Detail:
Title:  European journal of heart failure : journal of the Working Group on Heart Failure of the European Society of Cardiology     Volume:  -     ISSN:  1879-0844     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, PO Box 6492 St Kilda Rd Central, Melbourne, VIC 8008, Australia.
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