ArticleAmerican journal of respiratory cell and molecular biology2018
Role of the Aryl Hydrocarbon Receptor in Sugen 5416-induced Experimental Pulmonary Hypertension.
Article in American journal of respiratory cell and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
- Physiological interplay among obesity, male fertility, and aryl hydrocarbon receptor in human and mice: A mini review.Open veterinary journal · 2026Review
- Tryptophan metabolism: a potential link between the gut microbiota and pulmonary vascular remodeling in pulmonary hypertension.Frontiers in cellular and infection microbiology · 2026Review
- Long-term outcomes of Qing-Dai-induced pulmonary arterial hypertension.ERJ open research · 2025Article
- eNAMPT/TLR4 signaling drives PAH cellular phenotypic switching and lung vascular remodeling.Cell communication and signaling : CCS · 2025Article
- Biotransformation of ketamine in terminal in vivo experiments under chronic intermittent hypoxia conditions and the role of AhR.Archives of toxicology · 2025Article
- Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- Pulmonary artery smooth muscle cell pyroptosis promotes the proliferation of PASMCs by paracrine IL‑1β and IL‑18 in monocrotaline‑induced pulmonary arterial hypertensive rats.Experimental and therapeutic medicine · 2024Article
- A comprehensive analysis of genes associated with hypoxia and cuproptosis in pulmonary arterial hypertension using machine learning methods and immune infiltration analysis:Frontiers in medicine · 2024Article
- Kynurenine pathway metabolism evolves with development of preclinical and scleroderma-associated pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Angiogenesis Redux: An Overall Protective Role of VEGF/KDR Signaling in the Microvasculature in Pulmonary Arterial Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Spatial and temporal resolution of metabolic dysregulation in the Sugen hypoxia model of pulmonary hypertension.Pulmonary circulation · 2023Article
- Skeletal Muscle Dysfunction in Experimental Pulmonary Hypertension.International journal of molecular sciences · 2022Article
- Single-cell RNA sequencing profiling of mouse endothelial cells in response to pulmonary arterial hypertension.Cardiovascular research · 2022Article
- Article
- Exploring the failing right ventricle in pulmonary hypertension by cardiac magnetic resonance: An in vivo study utilizing Macitentan.Pulmonary circulation · 2022Article
- Aryl Hydrocarbon Receptor in Oxidative Stress as a Double Agent and Its Biological and Therapeutic Significance.International journal of molecular sciences · 2022Review
- The Aryl Hydrocarbon Receptor (AHR): A Novel Therapeutic Target for Pulmonary Diseases?International journal of molecular sciences · 2022Review
- Pulmonary Arterial Hypertension: Emerging Principles of Precision Medicine across Basic Science to Clinical Practice.Reviews in cardiovascular medicine · 2022Article
- Sex and gender in pulmonary arterial hypertension.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Treatment-refractory ulcerative colitis responsive to indigo naturalis.BMJ open gastroenterology · 2021Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Rats dosed with the vascular endothelial growth factor inhibitor Sugen 5416 (Su), subjected to hypoxia, and then restored to normoxia have become a widely used model of pulmonary arterial hypertension (PAH). However, the mechanism by which Su exacerbates pulmonary hypertension is unclear. We investigated Su activation of the aryl hydrocarbon receptor (AhR) in human pulmonary artery smooth muscle cells (hPASMCs) and blood outgrowth endothelial cells (BOECs) from female patients with PAH. We also examined the effect of AhR on aromatase and estrogen levels in the lung. Protein and mRNA analyses demonstrated that CYP1A1 was very highly induced in the lungs of Su/hypoxic (Su/Hx) rats. The AhR antagonist CH223191 (8 mg/kg/day) reversed the development of PAH in this model in vivo and normalized lung CYP1A1 expression. Increased lung aromatase and estrogen levels in Su/Hx rats were also normalized by CH223191, as was AhR nuclear translocator (ARNT [HIF-1β]), which is shared by HIF-1α and AhR. Su reduced HIF-1α expression in hPASMCs. Su induced proliferation in BOECs and increased apoptosis in human pulmonary microvascular ECs and also induced translocation of AhR to the nucleus in hPASMCs. Under normoxic conditions, hPASMCs did not proliferate to Su. However, when grown in hypoxia (1%), Su induced hPASMC proliferation. In combination with hypoxia, Su is proliferative in hPASMCs and BOECs from patients with PAH, and Su/Hx-induced PAH in rats may be facilitated by AhR-induced CYP1A1, ARNT, and aromatase. Inhibition of AhR may be a novel approach to the treatment of pulmonary hypertension.
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