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 AND RESULTS: 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.