Document Detail


Cardiomyocyte hyperplasia after plasmid-mediated vascular endothelial growth factor gene transfer in pigs with chronic myocardial ischemia.
MedLine Citation:
PMID:  14978775     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: For over 40 years it has been proposed that cardiomyocyte hyperplasia may occur in hypertrophic human hearts. While this implies that heart myocytes can undergo cytokinesis, evidence of conventional cell division has been exceptionally reported. Recently, we found that gene transfer of vascular endothelial growth factor (VEGF) displays a mitogenic effect on adult cardiomyocytes. In the present study we searched for cardiomyocyte hyperplasia as evidence of VEGF-induced cardiomyocyte cytokinesis. METHODS: Three weeks after implanting an Ameroid constrictor at the origin of the left circumflex artery, 16 pigs were randomized to receive 10 direct intramyocardial injections of 3.8 mg of plasmid encoding for VEGF (pVEGF) or empty plasmid. Five weeks later, hearts were weighed, myocyte diameter was measured in tissue sections, and myocyte length and nuclei number were studied in isolated myocytes. A resting echocardiogram was performed immediately before reoperation and before sacrifice to evaluate global and regional left ventricular function. Investigators were blinded to the study groups and nature of the injectate until the end of data analysis. RESULTS: No heart weight differences existed between groups. However, in the ischemic myocardium, pVEGF-treated hearts had 22% more cardiomyocytes per unit volume and exhibited significantly more oligonucleated (1 or 2 nuclei) cardiomyocytes than hearts receiving empty plasmid. CONCLUSIONS: In pigs with chronic myocardial ischemia, VEGF gene transfer induced cardiomyocyte cytokinesis, as revealed by cardiomyocyte hyperplasia. Our finding extends the previously reported mitogenic effect of VEGF on adult cardiomyocytes and supports the hypothesis that VEGF may have a therapeutic role in diseases characterized by myocardial cell loss.
Authors:
Rubén Laguens; Patricia Cabeza Meckert; Gustavo Vera Janavel; Andrea De Lorenzi; Elena Lascano; Jorge Negroni; Héctor Del Valle; Luis Cuniberti; Verónica Martínez; Eduardo Dulbecco; Carlos Melo; Nahuel Fernández; Marcelo Criscuolo; Alberto Crottogini
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The journal of gene medicine     Volume:  6     ISSN:  1099-498X     ISO Abbreviation:  J Gene Med     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-02-23     Completed Date:  2004-10-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815764     Medline TA:  J Gene Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  222-7     Citation Subset:  IM    
Copyright Information:
Copyright 2004 John Wiley & Sons, Ltd.
Affiliation:
Department of Pathology, Favaloro University, Buenos Aires, Argentina.
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MeSH Terms
Descriptor/Qualifier:
Animals
Gene Transfer Techniques*
Myocardial Ischemia / therapy*
Myocytes, Cardiac / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Swine / metabolism
Vascular Endothelial Growth Factor A / genetics*,  metabolism
Chemical
Reg. No./Substance:
0/Vascular Endothelial Growth Factor A

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