Document Detail

Transcriptional and functional adaptations of human endothelial cells to physiological chronic low oxygen.
MedLine Citation:
PMID:  23536375     Owner:  NLM     Status:  MEDLINE    
Endothelial cells chronically reside in low-O2 environments in vivo (2%-13% O2), which are believed to be critical for cell homeostasis. To elucidate the roles of this physiological chronic normoxia in human endothelial cells, we examined transcriptomes of human umbilical vein endothelial cells (HUVECs), proliferation and migration of HUVECs in response to fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA), and underlying signaling mechanisms under physiological chronic normoxia. Immediately after isolation, HUVECs were cultured steadily under standard cell culture normoxia (SCN; 21% O2) or physiological chronic normoxia (PCN; 3% O2) up to 25 days. We found that PCN up-regulated 41 genes and down-regulated 21 genes, 90% of which differed from those previously reported from HUVECs cultured under SCN and exposed to acute low O2. Gene ontology analysis indicated that PCN-regulated genes were highly related to cell proliferation and migration, consistent with the results from benchtop assays that showed that PCN significantly enhanced FGF2- and VEGFA-stimulated cell proliferation and migration. Interestingly, preexposing the PCN cells to 21% O2 up to 5 days did not completely diminish PCN-enhanced cell proliferation and migration. These PCN-enhanced cell proliferations and migrations were mediated via augmented activation of MEK1/MEK2/ERK1/ERK2 and/or PI3K/AKT1. Importantly, these PCN-enhanced cellular responses were associated with an increase in activation of VEGFR2 but not FGFR1, without altering their expression. Thus, PCN programs endothelial cells to undergo dramatic changes in transcriptomes and sensitizes cellular proliferative and migratory responses to FGF2 and VEGFA. These PCN cells may offer a unique endothelial model, more closely mimicking the in vivo states.
Yi-Zhou Jiang; Kai Wang; Yan Li; Cai-Feng Dai; Ping Wang; Christina Kendziorski; Dong-Bao Chen; Jing Zheng
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-05-09
Journal Detail:
Title:  Biology of reproduction     Volume:  88     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-10     Completed Date:  2013-10-22     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  114     Citation Subset:  IM    
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MeSH Terms
Adaptation, Physiological / physiology*
Cell Hypoxia / physiology*
Cell Movement / drug effects,  physiology*
Cell Proliferation / drug effects
Cells, Cultured
Fibroblast Growth Factor 2 / pharmacology
Human Umbilical Vein Endothelial Cells / cytology,  drug effects,  metabolism*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction / drug effects,  physiology
Vascular Endothelial Growth Factor A / pharmacology
Grant Support
Reg. No./Substance:
0/Vascular Endothelial Growth Factor A; 103107-01-3/Fibroblast Growth Factor 2; EC Proteins c-akt; EC Protein Kinase 1; EC Protein Kinase 3

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