Address for Correspondence:

D ow nloaded from DOI: 10.1161/CIRCULATIONAHA.113.002336 2 After the occlusion of a nutritive blood vessel, muscle undergoes a continuum of molecular, cellular and extracellular responses that determine the fate of the ischemic tissue. During the latter phase of tissue healing, the different processes involved in new vessels formation, including angiogenesis, take place and represent an integral component of tissue remodeling which control the extent of ischemic injury. Angiogenesis is a complex process requiring the coordinated regulation of many activating and inhibitory pathways in which vascular endothelial growth factor (VEGF)-mediated endothelial cells (EC) migration and proliferation play an important role. VEGF acts, at least in part, through interaction with its VEGF receptor 2, also known as kinase insert domain receptor (KDR) in human or fetal liver kinase 1 (Flk1) in murine. Although the signaling pathways lying downstream VEGF-mediated KDR/Flk1 activation hav