The impaired hindlimb revascularization of Id1+/−, Id3−/− mutant supports a role for bone-marrow derived progenitor cells in physiologic neovascularization

Abstract

Abstract Introduction: Increasing evidence suggests the importance of bone-marrow derived progenitor cells in angiogenesis. However, the exact role of the progenitor cells in hindlimb revascularization is unknown. In order to determine if endothelial progenitor cells are necessary for hindlimb revascularization, we used Id1+/−, Id3−/− mutant mouse model, that has previously been described to have impaired mobilization of bone-marrow derived endothelial progenitor cells, and therefore fails to vascularize tumor and matrigel implants. Methods: Hindlimb ischemia was induced in both Id mutant and C57Bl/6 mice by excision of the left femoral artery. Hindlimb perfusion recovery was serially measured by laser doppler perfusion imaging scanning at 3,7,14,21 and 28 days after induction of ischemia. Hindlimb muscle was harvested 7 days after inducion of ischemia, and was analyzed by histology. Results: Throughout the course of recovery, Id mutants exhibited lower blood flow than that of the control mice. At post-operative day 28, the ratio of ischemic/normal blood flow in the mutants (0.370 +/− 0.050) indicated significantly lower hindlimb perfusion compared with that of the control (0.589 +/− 0.052, P Conclusions: Hindlimb revascularization is significantly impaired in Id mutnt mice, supporting a role for bone-marrow derived progenitor cells in physiologic neovascularization. These results have important implication for development of therapy to treat critical limb ischemia.