Document Detail


Hypoxia upregulates PGI-synthase and increases PGI₂ release in human vascular cells exposed to inflammatory stimuli.
MedLine Citation:
PMID:  21296955     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypoxia affects vascular function and cell metabolism, survival, growth, and motility; these processes are partially regulated by prostanoids. We analyzed the effect of hypoxia and inflammation on key enzymes involved in prostanoid biosynthesis in human vascular cells. In human vascular smooth muscle cells (VSMC), hypoxia and interleukin (IL)-1β synergistically increased prostaglandin (PG)I₂ but not PGE₂ release, thereby increasing the PGI₂/PGE₂ ratio. Concomitantly, these stimuli upregulated cyclooxygenase-2 (COX-2) expression (mRNA and protein) and COX activity. Interestingly, hypoxia enhanced PGI-synthase (PGIS) expression and activity in VSMC and human endothelial cells. Hypoxia did not significantly modify the inducible microsomal-PGE-synthase (mPGES)-1. Hypoxia-inducible factor (HIF)-1α-silencing abrogated hypoxia-induced PGIS upregulation. PGIS transcriptional activity was enhanced by hypoxia; however, the minimal PGIS promoter responsive to hypoxia (-131 bp) did not contain any putative hypoxia response element (HRE), suggesting that HIF-1 does not directly drive PGIS transcription. Serial deletion and site-directed mutagenesis studies suggested several transcription factors participate cooperatively. Plasma levels of the stable metabolite of PGI₂ and PGIS expression in several tissues were also upregulated in mice exposed to hypoxia. These data suggest that PGIS upregulation is part of the adaptive response of vascular cells to hypoxic stress and could play a role in counteracting the deleterious effect of inflammatory stimuli.
Authors:
Mercedes Camacho; Cristina Rodríguez; Anna Guadall; Sonia Alcolea; Mar Orriols; José-Román Escudero; José Martínez-González; Luis Vila
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-02-04
Journal Detail:
Title:  Journal of lipid research     Volume:  52     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-24     Completed Date:  2011-06-23     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  720-31     Citation Subset:  IM    
Affiliation:
Angiology, Vascular Biology, and Inflammation Laboratory, Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cell Hypoxia / genetics,  physiology*
Cells, Cultured
Culture Media, Conditioned / pharmacology
Cyclooxygenase 2 / metabolism
Dinoprostone / metabolism
Endothelial Cells / drug effects,  enzymology,  metabolism
Epoprostenol / metabolism*
Humans
Interleukin-1beta / pharmacology*
Male
Mice
Mice, Inbred C57BL
Muscle, Smooth, Vascular / cytology*
Myocytes, Smooth Muscle / drug effects,  enzymology*,  metabolism*
Polymerase Chain Reaction
Promoter Regions, Genetic / genetics
Prostaglandin-Endoperoxide Synthases / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Interleukin-1beta; 35121-78-9/Epoprostenol; 363-24-6/Dinoprostone; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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