ArticleAmerican journal of physiology. Lung cellular and molecular physiology2018
Endothelial HIF-2α contributes to severe pulmonary hypertension due to endothelial-to-mesenchymal transition.
Article in American journal of physiology. Lung cellular and molecular physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers.
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170 citing papers in PubMed, 178 citations in OpenAlex.
- SNAI2/SLUG: a key regulator of endothelial-to-mesenchymal transition and vascular remodeling in cardiovascular diseases.Journal of cardiothoracic surgery · 2026Review
- Group 3 Pulmonary Hypertension: Mechanistic Insights, Clinical Challenges, and Evolving Therapies.Journal of clinical medicine · 2026Review
- Stem cell factor regulates endothelial HIF-2α expression during hypoxia-driven pathological angiogenesis.BMB reports · 2026Article
- Post-translational modification crosstalk in pulmonary arterial hypertension: mechanisms and therapeutic implications.Molecular biology reports · 2026Review
- Poly-Pharmacologic Disruption of the Proliferative-to-Mesenchymal Fate Branch Point Reverses EndMT and Pulmonary Hypertension.Research square · 2026Article
- Variation inCirculation research · 2026Article
- Pulmonary Hypertension Molecular Switch: HIF Signaling Pathway.Pulmonary circulation · 2026Review
- Vein graft failure: Pathophysiology, detection, prevention and emerging therapeutic strategies.Pharmacological reviews · 2026Review
- Ubiquitination of Smad2 by Smurf1 inhibits endothelial-to-mesenchymal transition in human coronary artery endothelial cells.Scientific reports · 2026Article
- Heart-Lung Interactions in Pulmonary Hypertension due to Heart Failure With Preserved Ejection Fraction.Comprehensive physiology · 2026Review
- Endothelial-to-Mesenchymal Transition Mechanisms in Vascular Remodeling of Pulmonary Hypertension.International journal of molecular sciences · 2026Review
- From Heterogeneity to Plasticity: Endothelial Dynamics in Lung Disease.Pulmonary circulation · 2026Review
- Mitral stenosis severity and the hypoxic response: potential role of hypoxia-inducible factor-2α - a cross-sectional study.BMC cardiovascular disorders · 2026Article
- The effect of mitoTEMPO on the development of hypoxia-induced pulmonary hypertension in male mice.Physiological reports · 2026Article
- Altitude hypoxia and hypoxemia: pathogenesis and management.Signal transduction and targeted therapy · 2026Review
- Mechanisms Underlying Altitude-Induced and Group 3 Pulmonary Hypertension.International journal of molecular sciences · 2026Review
- Regulatory T cells in hypoxic environments.Frontiers in immunology · 2026Review
- A phytotherapeutic approach to hinder the resistance against clindamycin by MRSA:Future science OA · 2025Article
- eNAMPT/TLR4 signaling drives PAH cellular phenotypic switching and lung vascular remodeling.Cell communication and signaling : CCS · 2025Article
- Toward precision medicine in COPD: phenotypes, endotypes, biomarkers, and treatable traits.Respiratory research · 2025Review
110 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 2 institutions in 2 countries.
Funding
Abstract
Pulmonary vascular remodeling characterized by concentric wall thickening and intraluminal obliteration is a major contributor to the elevated pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension (IPAH). Here we report that increased hypoxia-inducible factor 2α (HIF-2α) in lung vascular endothelial cells (LVECs) under normoxic conditions is involved in the development of pulmonary hypertension (PH) by inducing endothelial-to-mesenchymal transition (EndMT), which subsequently results in vascular remodeling and occlusive lesions. We observed significant EndMT and markedly increased expression of SNAI, an inducer of EndMT, in LVECs from patients with IPAH and animals with experimental PH compared with normal controls. LVECs isolated from IPAH patients had a higher level of HIF-2α than that from normal subjects, whereas HIF-1α was upregulated in pulmonary arterial smooth muscle cells (PASMCs) from IPAH patients. The increased HIF-2α level, due to downregulated prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase that promotes HIF-2α degradation, was involved in enhanced EndMT and upregulated SNAI1/2 in LVECs from patients with IPAH. Moreover, knockdown of HIF-2α (but not HIF-1α) with siRNA decreases both SNAI1 and SNAI2 expression in IPAH-LVECs. Mice with endothelial cell (EC)-specific knockout (KO) of the PHD2 gene, egln1 (egln1
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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.