Objective      To determine the effect of human receptor activity modified protein 1 (hRAMP1)-overexpressing mese

nchymal stem cells （MSCs） by adenovirus vector on infarcted related revascularization and its potential mechanism in a rabbit model of myocardial infarction.       Methods        Thirty 4- to 5-month-old health male rabbits were developed to myocardial infarction (MI) and reperfusion models by ligating left ventricular branch of coronary artery for 60 min

and then divided into MSC

hRAMP1

group (n=10)

MSC

null

group (n=10) and control group (n=10) according to whether they were received intravenously injection of MSCs transfected with adenovirus vector encoding hRAMP1 gene and enhanced green fluorescent protein (EGFP)

of MSCs transfected with adenovirus vector encoding only EGFP without hRAMP1 gene or of equally volume of phosphate buffered saline (PBS).The protein expression of vascular endothelial growth factor （VEGF） and hepatocyte growth factor （HGF） in infracted myocardium were measured by Western blotting in 2 weeks following MI. MI was evaluated by TTC staining for infracted area

and capillary density in infarcted region and its border region were tested by anti-CD31 immunohistochemistry staining. VEGF and HGF levels in the supernatant were quantified by ELISA assay in 24 and 72 h after induction of CGRP in cultured MSCs.       Results       The levels of VEGF and HGF in the cultured supernatant of MSC

hRAMP1

group were significantly higher than in the supernatant of MSC

null

group when they were induced by CGRP for 72 h. Furthermore

there was a significant decrease in the area ratio of MI in MSC

hRAMP1

group than in MSC

null

and control group by TTC staining. Also

compared with MSC

null

and control groups

capillary density indicated by CD31-positive cells in the infarcted and border region was statistically augmented in MSC

hRAMP1

group by immunohistochemistry assay. The protein expression of VEGF and HGF detected by Western blotting were much higher in MSC

hRAMP1

group compared with MSC

null

and cont

rol group at 2 weeks following MSCs delivery.       Conclusion        Gene modified MSCs with hRAMP1 overexpression have the powerful potential to increase capillary density and improve revascularization through more secretion of VEGF and HGF in infarcted and border region.