Hypoxia upregulates PGI-synthase and increases PGI2 release in human vascular cells exposed to inflammatory stimuli
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 muscl...
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doaj-0336e03b921c49889c17fd2b23d6e8b92021-04-28T06:03:37ZengElsevierJournal of Lipid Research0022-22752011-04-01524720731Hypoxia upregulates PGI-synthase and increases PGI2 release in human vascular cells exposed to inflammatory stimuliMercedes Camacho0Cristina Rodríguez1Anna Guadall2Sonia Alcolea3Mar Orriols4José-Román Escudero5José Martínez-González6Luis Vila7Angiology, Vascular Biology, and Inflammation Laboratory, Institute of Biomedical Research (IIB-Sant Pau), Barcelona, SpainCardiovascular Research Center (CSIC-ICCC), Institute of Biomedical Research (IIB-Sant Pau), Barcelona, SpainCardiovascular Research Center (CSIC-ICCC), Institute of Biomedical Research (IIB-Sant Pau), Barcelona, SpainAngiology, Vascular Biology, and Inflammation Laboratory, Institute of Biomedical Research (IIB-Sant Pau), Barcelona, SpainCardiovascular Research Center (CSIC-ICCC), Institute of Biomedical Research (IIB-Sant Pau), Barcelona, SpainAngiology, Vascular Biology, and Inflammation Laboratory, Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Vascular Surgery Department, Institute of Biomedical Research (IIB-Sant Pau), Barcelona, SpainTo whom correspondence should be addressed. (J.M-G.); (L.V.) jmartinez@csic-iccc.orglvila@santpau.cat; Cardiovascular Research Center (CSIC-ICCC), Institute of Biomedical Research (IIB-Sant Pau), Barcelona, SpainTo whom correspondence should be addressed. (J.M-G.); (L.V.) jmartinez@csic-iccc.orglvila@santpau.cat; Angiology, Vascular Biology, and Inflammation Laboratory, Institute of Biomedical Research (IIB-Sant Pau), Barcelona, SpainHypoxia 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.http://www.sciencedirect.com/science/article/pii/S002222752040906Xcyclooxygenase-pathwayprostaglandin I-synthaseprostacyclin-synthaseprostacyclinsmooth muscle cellsendothelial cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mercedes Camacho Cristina Rodríguez Anna Guadall Sonia Alcolea Mar Orriols José-Román Escudero José Martínez-González Luis Vila |
spellingShingle |
Mercedes Camacho Cristina Rodríguez Anna Guadall Sonia Alcolea Mar Orriols José-Román Escudero José Martínez-González Luis Vila Hypoxia upregulates PGI-synthase and increases PGI2 release in human vascular cells exposed to inflammatory stimuli Journal of Lipid Research cyclooxygenase-pathway prostaglandin I-synthase prostacyclin-synthase prostacyclin smooth muscle cells endothelial cells |
author_facet |
Mercedes Camacho Cristina Rodríguez Anna Guadall Sonia Alcolea Mar Orriols José-Román Escudero José Martínez-González Luis Vila |
author_sort |
Mercedes Camacho |
title |
Hypoxia upregulates PGI-synthase and increases PGI2 release in human vascular cells exposed to inflammatory stimuli |
title_short |
Hypoxia upregulates PGI-synthase and increases PGI2 release in human vascular cells exposed to inflammatory stimuli |
title_full |
Hypoxia upregulates PGI-synthase and increases PGI2 release in human vascular cells exposed to inflammatory stimuli |
title_fullStr |
Hypoxia upregulates PGI-synthase and increases PGI2 release in human vascular cells exposed to inflammatory stimuli |
title_full_unstemmed |
Hypoxia upregulates PGI-synthase and increases PGI2 release in human vascular cells exposed to inflammatory stimuli |
title_sort |
hypoxia upregulates pgi-synthase and increases pgi2 release in human vascular cells exposed to inflammatory stimuli |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2011-04-01 |
description |
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. |
topic |
cyclooxygenase-pathway prostaglandin I-synthase prostacyclin-synthase prostacyclin smooth muscle cells endothelial cells |
url |
http://www.sciencedirect.com/science/article/pii/S002222752040906X |
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