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Enhanced endothelial progenitor cell mobilization and function through direct manipulation of hypoxia inducible factor‐1 α
Author(s) -
Zan Tao,
Li Hua,
Du Zijing,
Gu Bin,
Liu Kai,
Li Qingfeng
Publication year - 2015
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3091
Subject(s) - progenitor cell , homing (biology) , bone marrow , endothelial progenitor cell , angiogenesis , neovascularization , hypoxia (environmental) , stromal cell , vascular endothelial growth factor , cancer research , transfection , small hairpin rna , microbiology and biotechnology , medicine , immunology , apoptosis , stem cell , biology , chemistry , gene knockdown , cell culture , vegf receptors , ecology , genetics , biochemistry , organic chemistry , oxygen
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‐1 α (HIF‐1 α ). This study investigated the effects of directly manipulating HIF‐1 α on human EPCs in vitro . EPCs were isolated from human umbilical cord blood. Lentiviral vectors carrying HIF‐1 α and shRNA targeting HIF‐1 α were constructed for gene modification of the EPCs. Results demonstrated that after overexpression of HIF‐1 α 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‐1 α . These results indicate that direct HIF‐1 α manipulation over human EPCs is an effective method to promote EPC function and mobilization, thus suggest that drugs or reagents that elevate HIF‐1 α expression are capable of treating ischemic diseases. Copyright © 2015 John Wiley & Sons, Ltd.