ArticleHypertension (Dallas, Tex. : 1979)2020
Oral 15-Hydroxyeicosatetraenoic Acid Induces Pulmonary Hypertension in Mice by Triggering T Cell-Dependent Endothelial Cell Apoptosis.
Article in Hypertension (Dallas, Tex. : 1979), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Deletion of GPR39 Prevents Pulmonary Arterial Hypertension by Attenuating Hypoxia-Induced Aberrant Signaling.bioRxiv : the preprint server for biology · 2026Article
- Endothelial-to-Mesenchymal Transition Mechanisms in Vascular Remodeling of Pulmonary Hypertension.International journal of molecular sciences · 2026Review
- Associations Between Circulating Polyunsaturated Fatty Acids and Photoreceptor Measurement.Translational vision science & technology · 2026Article
- Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025Review
- 12/15-lipoxygenase mediates disturbed flow-induced endothelial dysfunction and atherosclerosis.Molecular medicine (Cambridge, Mass.) · 2025Article
- New insights into pulmonary arterial hypertension: interaction between PANoptosis and perivascular inflammatory responses.Apoptosis : an international journal on programmed cell death · 2025Review
- Omega-6 polyunsaturated fatty acids and their metabolites: a potential targeted therapy for pulmonary hypertension.Respiratory research · 2025Review
- Mechanisms of lung endothelial cell injury and survival in pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Review
- Intestinal IFNα4 promotes 15-HETE diet-induced pulmonary hypertension.Respiratory research · 2024Article
- Triazine herbicide prometryn alters epoxide hydrolase activity and increases cytochrome P450 metabolites in murine livers via lipidomic profiling.Scientific reports · 2024Article
- Emerging connectivity of programmed cell death pathways and pulmonary vascular remodelling during pulmonary hypertension.Journal of cellular and molecular medicine · 2024Review
- Lipidomic changes in a novel sepsis outcome-based analysis reveals potent pro-inflammatory and pro-resolving signaling lipids.Clinical and translational science · 2024Article
- The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension.Metabolites · 2023Review
- Unleashing the Potential of Nrf2: A Novel Therapeutic Target for Pulmonary Vascular Remodeling.Antioxidants (Basel, Switzerland) · 2023Review
- Lipid Mediators and Cytokines/Chemokines Display Differential Profiles in Severe versus Mild/Moderate COVID-19 Patients.International journal of molecular sciences · 2023Article
- GPR39 deorphanization: The long and winding road to eicosanoids and a crosstalk between GPR39 and hedgehog signaling in angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Pulmonary Vascular Remodeling in Pulmonary Hypertension.Journal of personalized medicine · 2023Review
- An Overview of Circulating Pulmonary Arterial Hypertension Biomarkers.Frontiers in cardiovascular medicine · 2022Review
- Carbonic anhydrase inhibition improves pulmonary artery reactivity and nitric oxide-mediated relaxation in sugen-hypoxia model of pulmonary hypertension.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Cardioprotective Effects of n-3 Polyunsaturated Fatty Acids: Orchestration of mRNA Expression, Protein Phosphorylation, and Lipid Metabolism in Pressure Overload Hearts.Frontiers in cardiovascular medicine · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
Pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased mean pulmonary arterial pressure. Elevated plasma and lung concentrations of oxidized lipids, including 15-hydroxyeicosatetraenoic acid (15-HETE), have been demonstrated in patients with PAH and animal models. We previously demonstrated that feeding mice with 15-HETE is sufficient to induce pulmonary hypertension, but the mechanisms remain unknown. RNA sequencing data from the mouse lungs on 15-HETE diet revealed significant activation of pathways involved in both antigen processing and presentation and T cell-mediated cytotoxicity. Analysis of human microarray from patients with PAH also identified activation of identical pathways compared with controls. We show that in both 15-HETE-fed mice and patients with PAH, expression of the immunoproteasome subunit 5 is significantly increased, which was concomitant with an increase in the number of CD8/CD69 (cluster of differentiation 8 / cluster of differentiation 69) double-positive cells, as well as pulmonary arterial endothelial cell apoptosis in mice. Human pulmonary arterial endothelial cells cultured with 15-HETE were more prone to apoptosis when exposed to CD8 cells. Cultured intestinal epithelial cells secreted more oxidized lipids in response to 15-HETE, which is consistent with accumulation of circulating oxidized lipids in 15-HETE-fed mice. Administration of an apoA-I (apolipoprotein A-I) mimetic peptide, Tg6F (transgenic 6F), which is known to prevent accumulation of circulating oxidized lipids, not only inhibited pulmonary arterial endothelial cell apoptosis but also prevented and rescued 15-HETE-induced pulmonary hypertension in mice. In conclusion, our results suggest that (1) 15-HETE diet induces pulmonary hypertension by a mechanism that involves oxidized lipid-mediated T cell-dependent pulmonary arterial endothelial cell apoptosis and (2) Tg6F administration may be a novel therapy for treating PAH.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.