title: Enhanced endothelial progenitor cell mobilization and function through direct manipulation of hypoxia inducible factor-1α.
abstract: Endothelial progenitor cells (EPCs) play a significant role in physiological and pathological hypoxia resistance and neovascularization processes. The ability to mobilize EPCs from bone marrow usually indicates a prognostic endpoint of several vascular diseases. Thus, it is of great value to study possible approaches for activating functional EPCs. The mobilization/homing of EPCs from bone marrow is signalled by stromal-derived factor-1 (SDF-1), which is regulated by the hypoxia-inducible factor-1α (HIF-1α). This study investigated the effects of directly manipulating HIF-1α on human EPCs in vitro. EPCs were isolated from human umbilical cord blood. Lentiviral vectors carrying HIF-1α and shRNA targeting HIF-1α were constructed for gene modification of the EPCs. Results demonstrated that after overexpression of HIF-1α by lentiviral transfection, the proliferative capacity of EPCs was elevated while the apoptosis was inhibited and vice versa. On the other hand, the expression of angiogenic-related cytokines including SDF-1 was upregulated on both gene and protein levels when EPCs were transfected with HIF-1α. These results indicate that direct HIF-1α manipulation over human EPCs is an effective method to promote EPC function and mobilization, thus suggest that drugs or reagents that elevate HIF-1α expression are capable of treating ischemic diseases.
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Tao
authors: T
authors: Zan
authors: Hua
authors: H
authors: Li
authors: Zijing
authors: Z
authors: Du
authors: Bin
authors: B
authors: Gu
authors: Kai
authors: K
authors: Liu
authors: Qingfeng
authors: Q
authors: Li
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D016207:Cytokines; D006023:Glycoproteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010455:Peptides; D034741:RNA, Small Interfering
keywords: angiogenesis; endothelial progenitor cells; hypoxia-inducible factor-1α; prolyl hydroxylase domain-2; stromal-derived factor-1