Vascular Endothelial Growth Factor-A Specifies Formation of Native Collaterals and Regulates Collateral Growth in Ischemia

The density of native (pre-existing) collaterals and their capacity to enlarge into large conduit arteries in ischemia (arteriogenesis) are major determinants of the severity of tissue injury in occlusive disease. Mechanisms directing arteriogenesis remain unclear. Moreover, nothing is known about how native collaterals form in healthy tissue. Evidence suggests VEGF, which is important in embryonic vascular patterning and ischemic angiogenesis, may contribute to native collateral formation and arteriogenesis. Therefore, we examined mice heterozygous for VEGF receptor-1 (VEGFR-1+/-), VEGF receptor-2 (VEGFR-2+/-), and over-expressing (VEGFhi/+) and under-expressing VEGF-A (VEGFlo/+). Recovery from hindlimb ischemia was followed for 21 days after femoral artery ligation. All statements below are p