ArticleAmerican journal of respiratory cell and molecular biology2020
Augmented Pulmonary Vasoconstrictor Reactivity after Chronic Hypoxia Requires Src Kinase and Epidermal Growth Factor Receptor Signaling.
Article in American journal of respiratory cell and molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Searching for Old and New Small-Molecule Protein Kinase Inhibitors as Effective Treatments in Pulmonary Hypertension-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Lung Single-Cell Transcriptomics Reveal Diverging Pathobiology and Opportunities for Precision Targeting in Scleroderma-Associated Versus Idiopathic Pulmonary Arterial Hypertension.Circulation. Genomic and precision medicine · 2025Article
- Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension.Drug design, development and therapy · 2024Article
- Expression and regulation of HIF-1a in hypoxic pulmonary hypertension: Focus on pathological mechanism and Pharmacological Treatment.International journal of medical sciences · 2024Review
- Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2023Article
- Role of histone lactylation interference RNA mFrontiers in cell and developmental biology · 2023Review
- Impact of Zinc on Oxidative Signaling Pathways in the Development of Pulmonary Vasoconstriction Induced by Hypobaric Hypoxia.International journal of molecular sciences · 2022Review
- Hypoxic pulmonary endothelial cells release epidermal growth factor leading to vascular smooth muscle cell arginase-2 expression and proliferation.Physiological reports · 2022Article
- Hypertension: Potential Player in Cardiovascular Disease Incidence in Preeclampsia.Cardiovascular toxicology · 2022Review
- Plasma human growth cytokines in children with vasovagal syncope.Frontiers in cardiovascular medicine · 2022Article
- Evaluating the therapeutic role of selected active compounds inFrontiers in pharmacology · 2022Article
- Systematic Understanding of Pathophysiological Mechanisms of Oxidative Stress-Related Conditions-Diabetes Mellitus, Cardiovascular Diseases, and Ischemia-Reperfusion Injury.Frontiers in cardiovascular medicine · 2021Review
- Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling.Antioxidants (Basel, Switzerland) · 2020Review
- Intermittent Hypoxia Augments Pulmonary Vasoconstrictor Reactivity through PKCβ/Mitochondrial Oxidant Signaling.American journal of respiratory cell and molecular biology · 2020Article
- Cholesterol: A Novel Regulator of Vasoreactivity in Pulmonary Arteries.American journal of respiratory cell and molecular biology · 2020Article
- Altered Lipid Domains Facilitate Enhanced Pulmonary Vasoconstriction after Chronic Hypoxia.American journal of respiratory cell and molecular biology · 2020Article
- Src and Epidermal Growth Factor Receptor: Novel Partners in Mediating Chronic Hypoxia-induced Pulmonary Artery Hypertension.American journal of respiratory cell and molecular biology · 2020Article
- Membrane depolarization is required for pressure-dependent pulmonary arterial tone but not enhanced vasoconstriction to endothelin-1 following chronic hypoxia.Pulmonary circulationArticle
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7 authors at 1 institution in 1 country.
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Abstract
Chronic hypoxia augments pressure- and agonist-induced pulmonary vasoconstriction through myofilament calcium sensitization. NADPH oxidases contribute to the development of pulmonary hypertension, and both epidermal growth factor receptor and Src kinases can regulate NADPH oxidase. We tested the hypothesis that Src-epidermal growth factor receptor (EGFR) signaling mediates enhanced vasoconstrictor sensitivity after chronic hypoxia through NADPH oxidase-derived superoxide generation. Protocols employed pharmacological inhibitors in isolated, pressurized rat pulmonary arteries to examine the contribution of a variety of signaling moieties to enhanced vascular tone after chronic hypoxia. Superoxide generation in pulmonary arterial smooth muscle cells was assessed using the fluorescent indicator dihydroethidium. Indices of pulmonary hypertension were measured in rats treated with the EGFR inhibitor gefitinib. Inhibition of NADPH oxidase, Rac1 (Ras-related C3 botulinum toxin substrate 1), and EGFR abolished pressure-induced pulmonary arterial tone and endothelin-1 (ET-1)-dependent calcium sensitization and vasoconstriction after chronic hypoxia. Consistently, chronic hypoxia augmented ET-1-induced superoxide production through EGFR signaling, and rats treated chronically with gefitinib displayed reduced right ventricular pressure and diminished arterial remodeling. Src kinases were also activated by ET-1 after chronic hypoxia and contributed to enhanced basal arterial tone and vasoconstriction in response to ET-1. A role for matrix metalloproteinase 2 to mediate Src-dependent EGFR activation is further supported by our findings. Our studies support a novel role for an Src kinase-EGFR-NADPH oxidase signaling axis to mediate enhanced pulmonary vascular smooth muscle Ca
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