Human Myeloid-Derived Growth Factor Induces a Pro-Angiogenic Response and Functional Recovery in a Mouse Model of Peripheral Artery Disease.

摘要

Myeloid-derived growth factor (MYDGF) is a monocyte- and macrophage-secreted protein with anti-apoptotic and pro-angiogenic properties that has demonstrated protective effects in models of myocardial ischemia, but its role in peripheral ischemic injury has not been evaluated. We investigated the effects of recombinant human MYDGF (hMYDGF) in a murine hindlimb ischemia model. Male C57BL/6 mice underwent femoral artery ligation and were treated with continuous subcutaneous infusion of recombinant hMYDGF, vehicle control, or vascular endothelial growth factor (VEGF) as a positive control. Limb perfusion was assessed longitudinally using laser speckle contrast imaging, and functional recovery was evaluated using standardized limb function scoring. Recombinant hMYDGF significantly improved blood flow recovery in the ischemic limb compared with vehicle at all post-surgical time points, achieving levels of perfusion comparable to VEGF. Improved perfusion translated into accelerated early functional recovery, with a greater proportion of recombinant hMYDGF-treated mice retaining normal toe flexion. Immunohistochemical analyses revealed significantly increased CD34+ endothelial cell staining in both quadriceps and gastrocnemius muscles in recombinant hMYDGF-treated mice, consistent with enhanced angiogenesis, while alpha-smooth muscle actin staining did not differ between groups. Collectively, these findings demonstrate that recombinant hMYDGF restores blood flow and accelerates functional recovery following ischemic injury, supporting its therapeutic potential for ischemic diseases.