title: Apelin/APJ signaling promotes hypoxia-induced proliferation of endothelial progenitor cells via phosphoinositide-3 kinase/Akt signaling.
abstract: Endothelial progenitor cells (EPCs) can adhere to the endothelium at sites of hypoxia/ischemia and participate in the formation of novel vessels through differentiating into endothelial cells (ECs). Apelin is an endogenous ligand for the G protein‑coupled receptor APJ, and apelin/APJ signaling has a role in cardiovascular function. The present study aimed to investigate the role of apelin/APJ signaling in the regulation of EPC proliferation under hypoxia. The results showed that hypoxia was able to induce EPC proliferation, accompanied with an upregulation of hypoxia‑inducible factor (HIF)‑1α as well as apelin/APJ signaling. Further investigation indicated that siRNA‑mediated knockdown of apelin or APJ expression attenuated the hypoxia‑induced proliferation of EPCs, suggesting that apelin/APJ signaling has an important role in hypoxia‑induced EPC proliferation. Moreover, the phosphoinositide‑3 kinase (PI3K)/Akt signaling pathway was found to be involved in the apelin/APJ‑mediated EPC proliferation under hypoxia. Based on these findings, the present study suggested that hypoxia‑induced upregulation of HIF‑1α promotes the expression of apelin and APJ, which further activate the downstream PI3K/Akt signaling pathway, a key promoter of EPC proliferation. In conclusion, the present study highlighted the role of apelin/APJ in the regulation of EPC proliferation, and apelin/APJ may therefore serve as a potential target for the prevention of hypoxic ischemic injury.
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Jingchang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Xinqun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Zhenfei
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000073861:Apelin; D000075244:Apelin Receptors; D015687:Cell Hypoxia; D049109:Cell Proliferation; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt