Transplanted mesenchymal stem cells (MSC) release soluble factors that 
contribute to cardiac repair and vascular regeneration. We hypothesized that 
overexpression of GATA-4 enhances the MSC secretome, thereby increasing cell 
survival and promoting postinfarction cardiac angiogenesis. MSCs harvested from 
male rat bone marrow were transduced with GATA-4 (MSC(GATA-4)) using the murine 
stem cell virus retroviral expression system; control cells were either 
nontransduced (MSC(bas)) or transduced with empty vector (MSC(Null)). Compared 
with these control cells, MSC(GATA-4) were shown by immunofluorescence, 
real-time PCR, and Western blotting to have higher expression of GATA-4. An 
increased expression of angiogenic factors in MSC(GATA-4) and higher MSC 
resistance against hypoxia were observed. Human umbilical vein endothelial cells 
(HUVEC) treated with MSC(GATA-4) conditioned medium exhibited increased 
formation of capillary-like structures and promoted migration, compared with 
HUVECs treated with MSC(Null) conditioned medium. MSC(GATA-4) were injected into 
the peri-infarct region in an acute myocardial infarction model in 
Sprague-Dawley rats developed by ligation of the left anterior descending 
coronary artery. Survival of MSC(GATA-4), determined by Sry expression, was 
increased at 4 days postengraftment. MSC(GATA-4)-treated animals showed 
significantly improved cardiac function as assessed by echocardiography. 
Furthermore, fluorescent microsphere and histological studies revealed increased 
blood flow and blood vessel density and reduced infarction size in 
MSC(GATA-4)-treated animals. We conclude that GATA-4 overexpression in MSCs 
increased both MSC survival and angiogenic potential in ischemic myocardium and 
may therefore represent a novel and efficient therapeutic approach for 
postinfarct remodeling.