ArticleThe American journal of pathology2013
TRPC4 inactivation confers a survival benefit in severe pulmonary arterial hypertension.
Article in The American journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- TRPC Channels as Mediators of Hypoxia-Induced Pulmonary Hypertension in Obstructive Sleep Apnea.International journal of molecular sciences · 2026Review
- Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- Pentastatin, a matrikine of the collagen IVα5, is a novel endogenous mediator of pulmonary endothelial dysfunction.American journal of physiology. Cell physiology · 2023Article
- Mechanosensitive channels in lung disease.Frontiers in physiology · 2023Review
- Article
- Role of Ion Channel Remodeling in Endothelial Dysfunction Induced by Pulmonary Arterial Hypertension.Biomolecules · 2022Review
- Role of Store-Operated CaBiomolecules · 2021Review
- Mechanosensitivity in Pulmonary Circulation: Pathophysiological Relevance of Stretch-Activated Channels in Pulmonary Hypertension.Biomolecules · 2021Review
- TRPC and TRPV Channels' Role in Vascular Remodeling and Disease.International journal of molecular sciences · 2020Review
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Development of an endothelial cell-restricted transgenic reporter rat: a resource for physiological studies of vascular biology.American journal of physiology. Heart and circulatory physiology · 2020Article
- Intracellular acidification facilitates receptor-operated TRPC4 activation through PLCδ1 in a CaThe Journal of physiology · 2020Article
- Treasure troves of pharmacological tools to study transient receptor potential canonical 1/4/5 channels.British journal of pharmacology · 2019Review
- Ion Channels in Pulmonary Hypertension: A Therapeutic Interest?International journal of molecular sciences · 2018Review
- Electrical Vagal Nerve Stimulation Ameliorates Pulmonary Vascular Remodeling and Improves Survival in Rats With Severe Pulmonary Arterial Hypertension.JACC. Basic to translational science · 2018Article
- Review
- Pulmonary vascular dysfunction secondary to pulmonary arterial hypertension: insights gained through retrograde perfusion.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Impaired Pulmonary Arterial Vasoconstriction and Nitric Oxide-Mediated Relaxation Underlie Severe Pulmonary Hypertension in the Sugen-Hypoxia Rat Model.The Journal of pharmacology and experimental therapeutics · 2018Article
- The Role of Transient Receptor Potential Channel 6 Channels in the Pulmonary Vasculature.Frontiers in immunology · 2017Review
- Endothelial Cell Reactive Oxygen Species and CaAdvances in experimental medicine and biology · 2017Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 3 countries.
Funding
Abstract
Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure with lumen-occluding neointimal and plexiform lesions. Activation of store-operated calcium entry channels promotes contraction and proliferation of lung vascular cells. TRPC4 is a ubiquitously expressed store-operated calcium entry channel, but its role in PAH is unknown. We tested the hypothesis that TRPC4 promotes pulmonary arterial constriction and occlusive remodeling, leading to right ventricular failure in severe PAH. Severe PAH was induced in Sprague-Dawley rats and in wild-type and TRPC4-knockout Fischer 344 rats by a single subcutaneous injection of SU5416 [SU (semaxanib)], followed by hypoxia exposure (Hx; 10% O2) for 3 weeks and then a return to normoxia (Nx; 21% O2) for 3 to 10 additional weeks (SU/Hx/Nx). Although rats of both backgrounds exhibited indistinguishable pulmonary hypertensive responses to SU/Hx/Nx, Fischer 344 rats died within 6 to 8 weeks. Normoxic and hypertensive TRPC4-knockout rats recorded hemodynamic parameters similar to those of their wild-type littermates. However, TRPC4 inactivation conferred a striking survival benefit, due in part to preservation of cardiac output. Histological grading of vascular lesions revealed a reduction in the density of severely occluded small pulmonary arteries and in the number of plexiform lesions in TRPC4-knockout rats. TRPC4 inactivation therefore provides a survival benefit in severe PAH, associated with a decrease in the magnitude of occlusive remodeling.
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Registered trials
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.