ArticleAmerican journal of physiology. Lung cellular and molecular physiology2012
Upregulation of osmo-mechanosensitive TRPV4 channel facilitates chronic hypoxia-induced myogenic tone and pulmonary hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 117 citations in OpenAlex.
- Cough hypersensitivity risk increases during heatwaves and can be reduced by inhalation of alkaline aerosols of endogenous ions.Scientific reports · 2026Article
- TRPV4 mediates aminoglycoside trafficking and ototoxicity without compromising antimicrobial efficacy.Cell death discovery · 2026Article
- The Potential Role of Calcium Channels in Pulmonary Hypertension.BioMed research international · 2026Review
- Integrative Genomics and Multi-Tissue Transcriptomics Identify Key Loci and Pathways for Hypoxia Tolerance in Grass Carp.Animals : an open access journal from MDPI · 2025Article
- Heat waves elevate risks of airway hypersensitivity that inhaled endogenous ions reduce.Research square · 2025Article
- Pathophysiology of Group 3 Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxia.International journal of molecular sciences · 2025Review
- TRPV4 Channel Modulators as Potential Drug Candidates for Cystic Fibrosis.International journal of molecular sciences · 2024Review
- Increased Susceptibility to Mechanical Stretch Drives the Persistence of Keloid Fibroblasts: An Investigation Using a Stretchable PDMS Platform.Biomedicines · 2024Article
- TRP Channels in Stroke.Neuroscience bulletin · 2024Review
- Role of transient receptor potential channels in the regulation of vascular tone.Drug discovery today · 2024Review
- ANO1, CaV1.2, and IP3R form a localized unit of EC-coupling in mouse pulmonary arterial smooth muscle.The Journal of general physiology · 2023Article
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Review
- Flipping Off and On the Redox Switch in the Microcirculation.Annual review of physiology · 2023Review
- Cell Confluence Modulates TRPV4 Channel Activity in Response to Hypoxia.Biomolecules · 2022Article
- Gestational and Lactational Iron Deficiency Anemia Impairs Myelination and the Neurovascular Unit in Infant Rats.Molecular neurobiology · 2022Article
- Endothelial TRPV4 channels in lung edema and injury.Current topics in membranes · 2022Review
- Potential of the TRPM7 channel as a novel therapeutic target for pulmonary arterial hypertension.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2022Review
- Hypoxia and the integrated stress response promote pulmonary hypertension and preeclampsia: Implications in drug development.Drug discovery today · 2021Review
- Mechanosensitivity in Pulmonary Circulation: Pathophysiological Relevance of Stretch-Activated Channels in Pulmonary Hypertension.Biomolecules · 2021Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Chronic hypoxia causes pulmonary hypertension with vascular remodeling, increase in vascular tone, and altered reactivity to agonists. These changes involve alterations in multiple Ca(2+) pathways in pulmonary arterial smooth muscle cells (PASMCs). We have previously shown that vanilloid (TRPV)- and melastatin-related transient receptor potential (TRPM) channels are expressed in pulmonary arteries (PAs). Here we found that TRPV4 was the only member of the TRPV and TRPM subfamilies upregulated in PAs of chronic hypoxic rats. The increase in TRPV4 expression occurred within 1 day of hypoxia exposure, indicative of an early hypoxic response. TRPV4 in PASMCs were found to be mechanosensitive. Osmo-mechanical stress imposed by hypotonic solution activated Ca(2+) transients; they were inhibited by TRPV4 specific short interfering RNA, the TRPV blocker ruthenium red, and the cytochrome P450 epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Consistent with TRPV4 upregulation, the Ca(2+) response induced by the TRPV4 agonist 4α-phorbol 12,13-didecanoate and hypotonicity was potentiated in hypoxic PASMCs. Moreover, a significant myogenic tone, sensitive to ruthenium red, was observed in pressurized endothelium denuded small PAs of hypoxic but not normoxic rats. The elevated basal intracellular Ca(2+) concentration in hypoxic PASMCs was also reduced by ruthenium red. In extension of these results, the development of pulmonary hypertension, right heart hypertrophy, and vascular remodeling was significantly delayed and suppressed in hypoxic trpv4(-/-) mice. These results suggest the novel concept that TRPV4 serves as a signal pathway crucial for the development of hypoxia-induced pulmonary hypertension. Its upregulation may provide a pathogenic feed-forward mechanism that promotes pulmonary hypertension via facilitated Ca(2+) influx, subsequently enhanced myogenic tone and vascular remodeling.
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Registered trials
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