Mechanism of hypoxic inducible pathway for vascular regeneration

Abstract

Background:Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor that plays a key role in the regulation of gene expression in response to hypoxia. We investigated that HIF-1α gene transduced endothelial progenitor cell (EPCs) established enhanced vascular development in severe ischemic hindlimb animals when transplanted in vivo. In this time, we focused the mechanism of over-expression of HIF-1α gene activity in vitro.Methods & Results:We isolated peripheral blood mononuclear cells from human volunteers, cultured through days 7, transducted adenovirus encoding HIF-1α gene (Tf/HIF-1α) and β-galactosidase transducted EPCs (Tf/β) gene as control to ex vivo expanded EPCs with previous condition, and evaluated proliferative activity, and migration activity, adhesion molecule, and apoptosis assay. 1) Tf/HIF-1α EPCs augmented cell proliferative activity and enhanced cell migration compared to Tf/β. 2) Tf/HIF-1α supported significantly more rolling and adhesion of EPCs compared to Tf/β on IL-1β activated HUVEC monolayer using dilution flow chamber. 3) Tf/HIF-1α EPC apoptosis was markedly reduced more than controls after gene transfer.Conclusion:This strategy will clear more some mechanism of hypoxic inducible pathway and will provide the potential application of gene therapy for vascular regeneration. [Jpn J Physiol 54 Suppl:S90 (2004)]