Foxc2 overexpression enhances benefit of endothelial progenitor cells for inhibiting neointimal formation by promoting CXCR4-dependent homing

Although endothelial progenitor cells (EPCs) are capable of reducing the postintervention complications and increasing ischemic neovascularization, the extent of EPCs homing was shown to be rather low in most clinical settings, greatly limiting the effectiveness of EPCs therapy. In the present study, we report that Foxc2 overexpression enhances the homing capacity of EPCs and thereby improves the EPCs-mediated therapeutic benefit after artery injury. Our results suggest that Foxc2 may hopefully become a novel therapeutic molecular target for improving therapeutic effectiveness of EPCs delivery. On the other hand, some risk factors for coronary artery disease impair CXCR4 signaling. For instance, EPCs from diabetes mellitus or coronary artery disease patients exhibited reduced CXCR4 expression and diminished the therapeutic potential of autologous transplantation. Up-regulation of CXCR4 signaling by Foxc2 overexpression might compensate for the reduced effects, and thereby improve the therapeutic efficacy of autologous EPCs transplantation.