ArticleJournal of lipid research2011
Hypoxia upregulates PGI-synthase and increases PGI₂ release in human vascular cells exposed to inflammatory stimuli.
Article in Journal of lipid research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Cyclooxygenase-dependent contribution to increased flow mediated dilatation following a week of repeated ischemic preconditioning.European journal of applied physiology · 2026Article
- Advanced treatment strategies for high-altitude pulmonary hypertension employing natural medicines: A review.Journal of pharmaceutical analysis · 2025Review
- NADPH Oxidase 4: Crucial for Endothelial Function under Hypoxia-Complementing Prostacyclin.Antioxidants (Basel, Switzerland) · 2024Article
- Molecular recognition and activation of the prostacyclin receptor by anti-pulmonary arterial hypertension drugs.Science advances · 2024Article
- Distinct profiles of oxylipid mediators in liver, lung, and placenta after maternal nano-TiOEnvironmental science. Advances · 2023Article
- Role of prostanoids, nitric oxide and endothelin pathways in pulmonary hypertension due to COPD.Frontiers in medicine · 2023Review
- Nanomaterial Inhalation During Pregnancy Alters Systemic Vascular Function in a Cyclooxygenase-Dependent Manner.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Prostaglandin regulation of type 2 inflammation: From basic biology to therapeutic interventions.European journal of immunology · 2021Review
- Involvement of the VEGF signaling pathway in immunosuppression and hypoxia stress: analysis of mRNA expression in lymphocytes mediating panting in Jersey cattle under heat stress.BMC veterinary research · 2021Article
- Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia.Scientific reports · 2021Article
- Prostanoids and Resolution of Inflammation - Beyond the Lipid-Mediator Class Switch.Frontiers in immunology · 2021Review
- GEO Data Sets Analysis Identifies COX-2 and Its Related Micro RNAs as Biomarkers for Non-Ischemic Heart Failure.Frontiers in pharmacology · 2020Article
- Inflammation increases MMP levels via PGEInternational journal of obesity (2005) · 2019Article
- Prostacyclin Analogue-Loaded Nanoparticles Attenuate Myocardial Ischemia/Reperfusion Injury in Rats.JACC. Basic to translational science · 2019Article
- Immune Modulation to Enhance Bone Healing-A New Concept to Induce Bone Using Prostacyclin to Locally Modulate Immunity.Frontiers in immunology · 2019Article
- Human cytochrome P450 enzymes 5-51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition - toxic effects and benefits.Drug metabolism reviews · 2018Review
- Article
- Prostaglandin terminal synthases as novel therapeutic targets.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2017Review
- Expression of IL-1α correlates with distant metastasis in patients with head and neck squamous cell carcinoma.Oncotarget · 2015Article
- Fatty acid binding protein-4 (FABP4) is a hypoxia inducible gene that sensitizes mice to liver ischemia/reperfusion injury.Journal of hepatology · 2015Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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