ArticleAmerican journal of respiratory and critical care medicine2018
Therapeutic Targeting of Vascular Remodeling and Right Heart Failure in Pulmonary Arterial Hypertension with a HIF-2α Inhibitor.
Article in American journal of respiratory and critical care medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 164 citations in OpenAlex.
- Randomized phase II dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2024Trial
- E2F1 Drives Endothelial Arterial Programming in Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2026Article
- Pulmonary Hypertension Molecular Switch: HIF Signaling Pathway.Pulmonary circulation · 2026Review
- The clinical landscape of HIF2α inhibitors in oncology.Nature reviews. Clinical oncology · 2026Review
- Iron and the lung: emerging roles of iron metabolism in pulmonary disease pathogenesis and therapy.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Cellular Signalling Networks in High Altitude Pulmonary Hypertension: From Canonical Pathways to Emerging Targets.Cell proliferation · 2026Review
- Mitral stenosis severity and the hypoxic response: potential role of hypoxia-inducible factor-2α - a cross-sectional study.BMC cardiovascular disorders · 2026Article
- First-in-class HIF-2α therapy in genitourinary oncology: Belzutifan from von Hippel-Lindau disease to advanced renal cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- First-in-class HIF-2α therapy in genitourinary oncology: Belzutifan from von Hippel-Lindau disease to advanced renal cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- Mechanisms Underlying Altitude-Induced and Group 3 Pulmonary Hypertension.International journal of molecular sciences · 2026Review
- Hypoxic microenvironment and pulmonary hypertension.Respiratory research · 2025Review
- Engineering HMGB1-derived Peptides to Unravel Sex-Specific Mechanisms in Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- Belzutifan-Associated Hypoxia: A Review of the Novel Therapeutic, Proposed Mechanisms of Hypoxia, and Management Recommendations.International journal of molecular sciences · 2025Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Single-Cell and Spatial Transcriptomics Identified Fatty Acid-Binding Proteins Controlling Endothelial Glycolytic and Arterial Programming in Pulmonary Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Iron Replacement Attenuates Hypoxic Pulmonary Hypertension by Remodeling Energy Metabolism via Regulating the HIF2α/Mitochondrial Complex I, III/ROS Axis.Biomolecules · 2025Article
- ARF6 as a Novel Activator of HIF-2α in Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- ARNT-dependent HIF-2α signaling protects cardiac microvascular barrier integrity and heart function post-myocardial infarction.Communications biology · 2025Article
- Changes in Macrophages in Pulmonary Hypertension: A Focus on High-altitude Pulmonary Hypertension.Anatolian journal of cardiology · 2025Review
- Biological pathways and mechanisms linking COPD and cardiovascular disease.Therapeutic advances in chronic disease · 2025Review
52 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
rationalePulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive vasoconstriction and obliterative vascular remodeling that leads to right heart failure (RHF) and death. Current therapies do not target vascular remodeling and RHF, and result in only modest improvement of morbidity and mortality.
objectivesTo determine whether targeting HIF-2α (hypoxia-inducible factor-2α) with a HIF-2α-selective inhibitor could reverse PAH and RHF in various rodent PAH models.
methodsHIF-2α and its downstream genes were evaluated in lung samples and pulmonary arterial endothelial cells and smooth muscle cells from patients with idiopathic PAH as well as various rodent PAH models. A HIF-2α-selective inhibitor was used in human lung microvascular endothelial cells and in Egln1 MEASUREMENTS AND MAIN
resultsUpregulation of HIF-2α and its target genes was observed in lung tissues and isolated pulmonary arterial endothelial cells from patients with idiopathic PAH and three distinct rodent PAH models. Pharmacological inhibition of HIF-2α by the HIF-2α translation inhibitor C76 (compound 76) reduced right ventricular systolic pressure and right ventricular hypertrophy and inhibited RHF and fibrosis as well as obliterative pulmonary vascular remodeling in Egln1
conclusionsThese findings demonstrate that pharmacological inhibition of HIF-2α is a promising novel therapeutic strategy for the treatment of severe vascular remodeling and right heart failure in patients with PAH.
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