ArticleCardiovascular research2016
HIF-2α-mediated induction of pulmonary thrombospondin-1 contributes to hypoxia-driven vascular remodelling and vasoconstriction.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 63 papers.
What it found
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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
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Who cites it
63 citing papers in PubMed, 100 citations in OpenAlex.
- Dexamethasone prophylaxis protects from acute high-altitude illness by modifying the peripheral blood mononuclear cell inflammatory transcriptome.Bioscience reports · 2023Trial
- Hypoxia Inducible Factor-2 Alpha and Prolinhydroxylase 2 Polymorphisms in Patients with Acute Respiratory Distress Syndrome (ARDS).International journal of molecular sciences · 2017Trial
- THBS4 Regulates Pulmonary Hypertension via TGF-β/SMAD2 Signaling.Hypertension (Dallas, Tex. : 1979) · 2026Article
- R213G-Mediated Redistribution of EC-SOD Protects Against Sugen-Hypoxia Pulmonary Hypertension in Mice.Pulmonary circulation · 2026Article
- Cellular Signalling Networks in High Altitude Pulmonary Hypertension: From Canonical Pathways to Emerging Targets.Cell proliferation · 2026Review
- Donation After Circulatory Death Islets are Comparable to Standard-of-Care Donation After Brain Death Islets: Analysis of 801 Consecutive Human Islet Isolations.Transplantation direct · 2026Article
- Review
- Oxidative Stress and Inflammation in Hypoxemic Respiratory Diseases and Their Comorbidities: Molecular Insights and Diagnostic Advances in Chronic Obstructive Pulmonary Disease and Sleep Apnea.Antioxidants (Basel, Switzerland) · 2025Review
- Hypoxia preconditioned plasma increases the expression of growth factors to accelerate diabetic wound healing by promoting angiogenesis.Scientific reports · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- CD47-mediated tumor microenvironment remodeling: a central mechanism in immune evasion.Acta biochimica et biophysica Sinica · 2025Review
- Regulating islet stress responses through CD47 activation.Diabetologia · 2025Article
- Monocytes and interstitial macrophages contribute to hypoxic pulmonary hypertension.The Journal of clinical investigation · 2025Article
- Macrophage-driven immunopathology in pulmonary arterial hypertension: from mechanisms to targeted therapies.Frontiers in immunology · 2025Review
- THBS1 mediates hypoxia driven EndMT in pulmonary hypertension.Pulmonary circulation · 2024Article
- Endothelial HIFα/PDGF-B to smooth muscle Beclin1 signaling sustains pathological muscularization in pulmonary hypertension.JCI insight · 2024Article
- Small-molecule α-lipoic acid targets ELK1 to balance human neutrophil and erythrocyte differentiation.Stem cell research & therapy · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Pericytes contribute to pulmonary vascular remodeling via HIF2α signaling.EMBO reports · 2024Article
- The causes of pulmonary hypertension and the benefits of aerobic exercise for pulmonary hypertension from an integrated perspective.Frontiers in physiology · 2024Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsHypoxic conditions stimulate pulmonary vasoconstriction and vascular remodelling, both pathognomonic changes in pulmonary arterial hypertension (PAH). The secreted protein thrombospondin-1 (TSP1) is involved in the maintenance of lung homeostasis. New work identified a role for TSP1 in promoting PAH. Nonetheless, it is largely unknown how hypoxia regulates TSP1 in the lung and whether this contributes to pathological events during PAH. METHODS AND
resultsIn cell and animal experiments, we found that hypoxia induces TSP1 in lungs, pulmonary artery smooth muscle cells and endothelial cells, and pulmonary fibroblasts. Using a murine model of constitutive hypoxia, gene silencing, and luciferase reporter experiments, we found that hypoxia-mediated induction of pulmonary TSP1 is a hypoxia-inducible factor (HIF)-2α-dependent process. Additionally, hypoxic tsp1(-/-) pulmonary fibroblasts and pulmonary artery smooth muscle cell displayed decreased migration compared with wild-type (WT) cells. Furthermore, hypoxia-mediated induction of TSP1 destabilized endothelial cell-cell interactions. This provides genetic evidence that TSP1 contributes to vascular remodelling during PAH. Expanding cell data to whole tissues, we found that, under hypoxia, pulmonary arteries (PAs) from WT mice had significantly decreased sensitivity to acetylcholine (Ach)-stimulated endothelial-dependent vasodilation. In contrast, hypoxic tsp1(-/-) PAs retained sensitivity to Ach, mediated in part by TSP1 regulation of pulmonary Kv channels. Translating these preclinical studies, we find in the lungs from individuals with end-stage PAH, both TSP1 and HIF-2α protein expression increased in the pulmonary vasculature compared with non-PAH controls.
conclusionsThese findings demonstrate that HIF-2α is clearly implicated in the TSP1 pulmonary regulation and provide new insights on its contribution to PAH-driven vascular remodelling and vasoconstriction.
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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.