Improved limb perfusion and neoangiogenesis after intramuscular erythropoietin infusion in experimental model of limb ischemia

摘要

Erythropoietin (EPO) is a hematopoietic cytokine which also enhances the mobilization of endothelial progenitor cells (EPCs) [1] and exerts a protective effect on endothelial cells in several vascular injury models [2]. In addition, neovascularization plays a role in diseases involving ischemia, including tumors, atherosclerotic plaques, and ischemic heart disease [3]. The angiopoietin (Ang)/Tie system has been reported to be critically involved in disease progression through the activation of signaling pathways that control angiogenic remodeling [4]. Although Ang-1 and Ang-2 share similar binding affinities for the Tie2 receptor (the tyrosine kinase with immunoglobulin and epidermal growth factor [EGF] homology domain 2 receptor), they have opposing effects on receptor activation. Ang-1 induces receptor phosphorylation and contributes to blood vessel stabilization by the recruitment of periendothelial cells [5]. Therefore, we sought to investigate the effects of erythropoietin administration on perfusion, neovascularization and angiogenic factors' expression in an experimental model of limb ischemia. More specifically, we aimed to assess its effects on blood flow and vascular endothelial growth factor (VEGF), Ang-2/Tie-2 expression in the ischemic limb.