ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
Endothelial HIF signaling regulates pulmonary fibrosis-associated pulmonary hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2018Guideline
- IGF2BP3 promotes early angiogenesis in pulmonary fibrosis by stabilizing HIF-1α.Molecular and cellular biochemistry · 2026Article
- Pulmonary hypertension associated with interstitial lung disease: a state-of-the-art review.The European respiratory journal · 2026Review
- Exploring the therapeutic landscape of pulmonary hypertension associated with interstitial lung disease, with a focus on idiopathic pulmonary fibrosis: a narrative review.Frontiers in pharmacology · 2026Review
- mRNA Vaccination for COVID-19 Lowers the Risk for Pulmonary Fibrosis Through GIP-10/Gal-3/HIF-1 Downregulation.Cureus · 2025Article
- New perspectives on the progression of pulmonary fibrosis: the cascade from aberrant microvascular endothelial cell activation to fibrosis.Frontiers in medicine · 2025Review
- A HIF-2α-dependentAnnals of translational medicine · 2024Article
- The causes of pulmonary hypertension and the benefits of aerobic exercise for pulmonary hypertension from an integrated perspective.Frontiers in physiology · 2024Review
- Unraveling the role of HIF and epigenetic regulation in pulmonary arterial hypertension: implications for clinical research and its therapeutic approach.Frontiers in medicine · 2024Review
- Long-term treatment of chronic kidney disease patients with anemia using hypoxia-inducible factor prolyl hydroxylase inhibitors: potential concerns.Pediatric nephrology (Berlin, Germany) · 2024Review
- Proteomics analysis of lung tissue reveals protein makers for the lung injury of adjuvant arthritis rats.Molecular medicine reports · 2023Article
- Pharmacology and Emerging Therapies for Group 3 Pulmonary Hypertension Due to Chronic Lung Disease.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Updated perspective of EPAS1 and the role in pulmonary hypertension.Frontiers in cell and developmental biology · 2023Review
- Effect of Hypoxia on Pulmonary Endothelial Cells from Bleomycin-Induced Pulmonary Fibrosis Model Mice.International journal of molecular sciences · 2022Article
- Contribution of Adiponectin/Carnitine Palmityl Transferase 1A-Mediated Fatty Acid Metabolism during the Development of Idiopathic Pulmonary Fibrosis.Oxidative medicine and cellular longevity · 2022Article
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- Effects of isometric contraction of the quadriceps on the hardness and blood flow in the infrapatellar fat pad.Journal of physical therapy science · 2021Article
- Article
- Idiopathic pulmonary fibrosis and pulmonary hypertension: Heracles meets the Hydra.British journal of pharmacology · 2021Review
- Study on the Potential Mechanism of Fructus Tribuli in the Treatment of Hypertensive Vascular Remodeling Based on Network Pharmacology and Molecular Docking.Evidence-based complementary and alternative medicine : eCAM · 2021Article
Corrections and comments
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Authors and funding
26 authors at 2 institutions in 1 country.
Funding
Abstract
Pulmonary hypertension (PH) complicating chronic parenchymal lung disease, such as idiopathic pulmonary fibrosis, results in significant morbidity and mortality. Since the hypoxia-inducible factor (HIF) signaling pathway is important for development of pulmonary hypertension in chronic hypoxia, we investigated whether HIF signaling in vascular endothelium regulates development of PH related to pulmonary fibrosis. We generated a transgenic model in which HIF is deleted within vascular endothelial cells and then exposed these mice to chronic intraperitoneal bleomycin to induce PH associated with lung fibrosis. Although no differences in the degree of fibrotic remodeling were observed, we found that endothelial HIF-deficient mice were protected against development of PH, including right ventricle and pulmonary vessel remodeling. Similarly, endothelial HIF-deficient mice were protected from PH after a 4-wk exposure to normobaric hypoxia. In vitro studies of pulmonary vascular endothelial cells isolated from the HIF-targeted mice and controls revealed that endothelial HIF signaling increases endothelial cell expression of connective tissue growth factor, enhances vascular permeability, and promotes pulmonary artery smooth muscle cell proliferation and wound healing ability, all of which have the potential to impact the development of PH in vivo. Taken together, these studies demonstrate that vascular endothelial cell HIF signaling is necessary for development of hypoxia and pulmonary fibrosis associated PH. As such, HIF and HIF-regulated targets represent a therapeutic target in these conditions.
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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.