GATA-4 is an angiogenic survival factor of the infarcted heart.
Circ Heart Fail
; 3(3): 440-50, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20200331
ABSTRACT
BACKGROUND:
Recent data suggest that GATA-4 is an antiapoptotic factor required for adaptive responses and a key regulator of hypertrophy and hypertrophy-associated genes in the heart. As a leading cause of chronic heart failure, reversal of postinfarction left ventricular remodeling represents an important target for therapeutic interventions. Here, we studied the role of GATA-4 as a mediator of postinfarction remodeling in rats. METHODS ANDRESULTS:
Myocardial infarction, caused by ligating the left anterior descending coronary artery, significantly decreased the DNA binding activity of GATA-4 at day 1, whereas at 2 weeks the GATA-4 DNA binding was significantly upregulated. To determine the functional role of GATA-4, peri-infarct intramyocardial delivery of adenoviral vector expressing GATA-4 was done before left anterior descending coronary artery ligation. Hearts treated with GATA-4 gene transfer exhibited significantly increased ejection fraction and fractional shortening. Accordingly, infarct size was significantly reduced. To determine the cardioprotective mechanisms of GATA-4, myocardial angiogenesis, rate of apoptosis, c-kit+ cardiac stemlike cells, and genes regulated by GATA-4 were studied. The number of capillaries and stemlike cells was significantly increased, and decreased apoptosis was observed.CONCLUSION:
These results indicate that the reversal of reduced GATA-4 activity prevents adverse postinfarction remodeling through myocardial angiogenesis, antiapoptosis, and stem cell recruitment. GATA-4-based gene transfer may represent a novel, efficient therapeutic approach for heart failure.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neovascularização Fisiológica
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Remodelação Ventricular
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Fator de Transcrição GATA4
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Insuficiência Cardíaca
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Infarto do Miocárdio
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article