ArticleThe American journal of pathology2016
Transient Receptor Potential Channel 4 Encodes a Vascular Permeability Defect and High-Frequency Ca(2+) Transients in Severe Pulmonary Arterial Hypertension.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- The Potential Role of Calcium Channels in Pulmonary Hypertension.BioMed research international · 2026Review
- OGG1 Preserves Endothelial-Dependent Vasodilation and Regulates the Frequency and Spatial Area of Endothelial Calcium Signals.Biomolecules · 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
- Article
- Substrate stiffness modulates migration and local intercellular membrane motion in pulmonary endothelial cell monolayers.American journal of physiology. Cell physiology · 2022Article
- Role of Ion Channel Remodeling in Endothelial Dysfunction Induced by Pulmonary Arterial Hypertension.Biomolecules · 2022Review
- Mechanosensitivity in Pulmonary Circulation: Pathophysiological Relevance of Stretch-Activated Channels in Pulmonary Hypertension.Biomolecules · 2021Review
- Inflammation in Pulmonary Arterial Hypertension.Advances in experimental medicine and biology · 2021Review
- Microparticles in systemic sclerosis: Potential pro-inflammatory mediators and pulmonary hypertension biomarkers.Respirology (Carlton, Vic.) · 2019Article
- 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
- Review
- Pulmonary vascular dysfunction secondary to pulmonary arterial hypertension: insights gained through retrograde perfusion.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Endothelial Cell Reactive Oxygen Species and CaAdvances in experimental medicine and biology · 2017Review
- Endothelial hyperpermeability in severe pulmonary arterial hypertension: role of store-operated calcium entry.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Combined hyperspectral imaging, monolayer stress microscopy, and S8 image analysis approaches for simultaneously interrogating cellular signals and biomechanics.Proceedings of SPIE--the International Society for Optical EngineeringArticle
- Biventricular diastolic dysfunction, thrombocytopenia, and red blood cell macrocytosis in experimental pulmonary arterial hypertension.Pulmonary circulationArticle
- The role of endothelial leak in pulmonary hypertension (2017 Grover Conference Series).Pulmonary circulationArticle
- Single cell cloning generates lung endothelial colonies with conserved growth, angiogenic, and bioenergetic characteristics.Pulmonary circulationArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The canonical transient receptor potential channel 4 (TRPC4) comprises an endothelial store-operated Ca(2+) entry channel, and TRPC4 inactivation confers a survival benefit in pulmonary arterial hypertension (PAH). Endothelial Ca(2+) signals mediated by TRPC4 enhance vascular permeability in vitro, but the contribution of TRPC4-dependent Ca(2+) signals to the regulation of endothelial permeability in PAH is poorly understood. We tested the hypothesis that TRPC4 increases vascular permeability and alters the frequency of endothelial Ca(2+) transients in PAH. We measured permeability in isolated lungs, and found that TRPC4 exaggerated permeability responses to thapsigargin in Sugen/hypoxia-treated PAH rats. We compared endothelial Ca(2+) activity of wild-type with TRPC4-knockout rats using confocal microscopy, and evaluated how Ca(2+) signals were influenced in response to thapsigargin and sequential treatment with acetylcholine. We found that thapsigargin-stimulated Ca(2+) signals were increased in PAH, and recovered by TRPC4 inactivation. Store depletion revealed bimodal Ca(2+) responses to acetylcholine, with both short- and long-duration populations. Our results show that TRPC4 underlies an exaggerated endothelial permeability response in PAH. Furthermore, TRPC4 increased the frequency of endothelial Ca(2+) transients in severe PAH, suggesting that TRPC4 provides a Ca(2+) source associated with endothelial dysfunction in the pathophysiology of PAH. This phenomenon represents a new facet of the etiology of PAH, and may contribute to PAH vasculopathy by enabling inflammatory mediator flux across the endothelial barrier.
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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.