Targeted Disruption of Fgf2 Impairs Blood Flow Control in the Posterior Gracilis During Revascularization

Abstract

Following induction of ischemia through ligation of the femoral-saphenous artery & vein, the mouse hindlimb undergoes revascularization to re-establish perfusion to the affected area. Because fibroblast growth factor 2 (FGF2), a potent vascular cell mitogen, is upregulated during the first week following ligation, it was thought that FGF2 plays an important role in revascularization. However, using Fgf2 null mice we found that FGF2 is not necessary for vascular growth during revascularization, as determined by microangiographic assessment of collateralization and histological assessment of arteriolarization and angiogenesis. Instead, we found that FGF2 is necessary for maintaining the capacity for blood flow control during revascularization; reactive hyperemia, following acute iliac artery occlusion, was absent at day 14 following ligation. To evaluate the role of FGF2 in maintaining the capacity for blood flow control in specific vascular beds, we developed a fluorescent microsphere-based approach to measure blood flow in individual skeletal muscles, before and after electrical stimulation. Preliminary experiments with Fgf2 null mice demonstrate that functional hyperemia is absent in the posterior gracilis, but not in the anterior gracilis at day 14 following ligation. Additionally, preliminary gene expression analysis of the posterior gracilis muscle at day 14 following ligation demonstrates that the vasodilating ADP receptor (P2Y1) is down-regulated by nearly four fold as compared to wild type mice. This work was funded by HL-67067 and HL-0729-27.