The role of VEGFR1 on angiogenesis in ischemic tissue

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Vascular endothelial growth factor (VEGF) is essential for developmental and pathological angiogenesis. Two VEGF receptors tyrosine kinase have been identified, VEGFR1 and VEGFR2. These two receptors are involved in angiogenesis but the molecular base of their actions is not well understood. Here we report that in murine ischemic hind limb model and tumor implanted model using deletion of domain of VEGFR1 decreased the recovery from ischemic condition. VEGFR1 TK-/- mice exhibited delayed blood flow recovery from ischemia and impaired angiogenesis compared to wild type mice. Furthemore, compared to wild type mice, plasma level of stem cell actor (SCF), stromal derived factor-1 (SDF-1) and pro-MMP-9 were decreased in VEGFR1TK-/-. Bone marrow derived CXCR4+VEGFR1+cells were significantly decreased in VEGFR1TK-/- mice compared to WT. Wild type mice transplanted VEGFR1 TK-/-bone marrow decreased the recovery from ischemic condition compared to wild type mice transplanted with wild type mice. These results suggested that the VEGFR1 TK signaling modulates the mobilization of bone marrow cells to ischemic muscle