Gene expression profiles in endothelial progenitor cells exposed to hypoxia

Abstract

Hypoxia is known to play an important role in neovascularization through recruit endothelial progenitor cells (EPCs) from bone marrow or peripheral blood to injury tissue. However, the mechanism of the effect of hypoxia on angiogenic function of EPC is not fully understood. To identify and analyze genes induced by hypoxia in EPCs, we used microarray gene expression profiling. We also compared gene expression patterns in EPC with those in human umbilical vein endothelial cells (HUVECs). The expression of 338 genes was up‐regulated in EPCs exposed to hypoxia. In EPCs, hypoxic insult up‐regulated 339 genes including angiogenesis associated genes such as adhesion molecules, angiopoietin 2, neuropilin 1 and plexin A2. Among these genes, induction of genes encoding neuropilin 1 and plexin A2 was confirmed by real‐time quantitative polymerase chain reaction (PCR). In addition, we found that hypoxia remarkably increased the ability of EPCs to form tubelike networks on matrigel. From these results, it is suggested that hypoxia may increase angiogenic function of EPCs in neovascularization through up‐regulation of neuropilin 1, plexin A2. This work was supported by grant from the development of cell therapy manufacturing technology.