Key result
Peri-infarct intramyocardial delivery of GATA-4 via adenoviral vector significantly increased ejection fraction and fractional shortening, and reduced infarct size in rats.
Why the study?
Does GATA-4 gene transfer improve cardiac function and reduce infarct size in rats with myocardial infarction?
Does GATA-4 gene transfer improve cardiac function and reduce infarct size in rats with myocardial infarction?
GATA-4 gene transfer prevents adverse postinfarction remodeling and improves cardiac function in a rat model of myocardial infarction.
Extends GATA-4 as a target in post-MI remodeling; leaves open translation beyond rodent models.
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.
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Rysä et al. (2010) studied Myocardial infarction. Peri-infarct intramyocardial delivery of adenoviral vector expressing GATA-4 was evaluated on Ejection fraction, fractional shortening, and infarct size. Peri-infarct intramyocardial delivery of GATA-4 via adenoviral vector significantly increased ejection fraction and fractional shortening, and reduced infarct size in rats.
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