Myeloid-Derived Growth Factor Improves Endothelial Progenitor Cell Function and Angiogenesis in Mice With Diabetic Hindlimb Ischemia by Activating Akt/HIF-1α Signalling Pathway.

Myeloid-derived growth factor (MYDGF) offers new insights into inflammation and endothelial function, yet its role in endothelial progenitor cells (EPCs) and diabetes-related hindlimb ischemia (DLI) remains unclear. In this study, we found that MYDGF depletion impaired the angiogenic function of EPCs, leading to reduced vascularisation and decreased blood flow in diabetic mice with hindlimb ischemia. Conversely, treatment with adeno-associated virus-mediated MYDGF restored vascularisation and improved blood perfusion. In vitro, treatment with recombinant MYDGF attenuated EPC dysfunction, apoptosis and inflammatory responses. Mechanistic studies revealed that these protective effects were mediated via the AKT/HIF-1α pathway, and silencing HIF-1α abrogated the benefits of MYDGF both in vivo and in vitro. Together, these findings identified MYDGF as a potential therapeutic target for DLI.