ArticleJournal of the American Heart Association2013
Arachidonic acid-induced dilation in human coronary arterioles: convergence of signaling mechanisms on endothelial TRPV4-mediated Ca2+ entry.
Article in Journal of the American Heart Association, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 81 citations in OpenAlex.
- An update on regulation of the polymodal TRPV4 channel by protein phosphorylation.Channels (Austin, Tex.) · 2026Review
- The Emerging Role of Endothelial Ion Channels in the Control of Human Microcirculation.International journal of molecular sciences · 2026Review
- Effects of SGLT2 inhibitors on ion channels in heart failure: focus on the endothelium.Basic research in cardiology · 2025Review
- Inflammation-induced TRPV4 channels exacerbate blood-brain barrier dysfunction in multiple sclerosis.Journal of neuroinflammation · 2024Article
- Single-Cell RNA-Seq Reveals Coronary Heterogeneity and Identifies CD133Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Independent endothelial functions of PIEZO1 and TRPV4 in hepatic portal vein and predominance of PIEZO1 in mechanical and osmotic stress.Liver international : official journal of the International Association for the Study of the Liver · 2023Article
- WAO-ARIA consensus on chronic cough - Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways.The World Allergy Organization journal · 2021Review
- Functional Interaction between Transient Receptor Potential V4 Channel and Neuronal Calcium Sensor 1 and the Effects of Paclitaxel.Molecular pharmacology · 2021Article
- Calcium-Dependent Ion Channels and the Regulation of Arteriolar Myogenic Tone.Frontiers in physiology · 2021Review
- The Transient Receptor Potential Vanilloid 4 Channel and Cardiovascular Disease Risk Factors.Frontiers in physiology · 2021Review
- Role of Transient Receptor Potential Vanilloid 4 in Vascular Function.Frontiers in molecular biosciences · 2021Review
- Association of the sEH gene promoter polymorphisms and haplotypes with preeclampsia.Journal of medical biochemistry · 2020Article
- Transcriptome Profile of Next Generation Sequence Data Related to Inflammation on Nasopharyngeal Carcinoma Cases in Indonesia.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Endothelial CaThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2020Review
- Ablation of Endothelial TRPV4 Channels Alters the Dynamic CaInternational journal of molecular sciences · 2020Article
- TRPV4 Protects the Lung from Bacterial Pneumonia via MAPK Molecular Pathway Switching.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Role of macrophage TRPV4 in inflammation.Laboratory investigation; a journal of technical methods and pathology · 2020Review
- Endothelial TRPV4 channels and vasodilator reactivity.Current topics in membranes · 2020Review
- Novel mechanisms regulating endothelial barrier function in the pulmonary microcirculation.The Journal of physiology · 2019Review
- Transient receptor potential vanilloid 4 (TRPV4) activation by arachidonic acid requires protein kinase A-mediated phosphorylation.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundArachidonic acid (AA) and/or its enzymatic metabolites are important lipid mediators contributing to endothelium-derived hyperpolarizing factor (EDHF)-mediated dilation in multiple vascular beds, including human coronary arterioles (HCAs). However, the mechanisms of action of these lipid mediators in endothelial cells (ECs) remain incompletely defined. In this study, we investigated the role of the transient receptor potential vanilloid 4 (TRPV4) channel in AA-induced endothelial Ca(2+) response and dilation of HCAs. METHODS AND
resultsAA induced concentration-dependent dilation in isolated HCAs. The dilation was largely abolished by the TRPV4 antagonist RN-1734 and by inhibition of endothelial Ca(2+)-activated K(+) channels. In native and TRPV4-overexpressing human coronary artery ECs (HCAECs), AA increased intracellular Ca(2+) concentration ([Ca(2+)]i), which was mediated by TRPV4-dependent Ca(2+) entry. The AA-induced [Ca(2+)]i increase was inhibited by cytochrome P450 (CYP) inhibitors. Surprisingly, the CYP metabolites of AA, epoxyeicosatrienoic acids (EETs), were much less potent activators of TRPV4, and CYP inhibitors did not affect EET production in HCAECs. Apart from its effect on [Ca(2+)]i, AA induced endothelial hyperpolarization, and this effect was required for Ca(2+) entry through TRPV4. AA-induced and TRPV4-mediated Ca(2+) entry was also inhibited by the protein kinase A inhibitor PKI. TRPV4 exhibited a basal level of phosphorylation, which was inhibited by PKI. Patch-clamp studies indicated that AA activated TRPV4 single-channel currents in cell-attached and inside-out patches of HCAECs.
conclusionsAA dilates HCAs through a novel mechanism involving endothelial TRPV4 channel-dependent Ca(2+) entry that requires endothelial hyperpolarization, PKA-mediated basal phosphorylation of TRPV4, and direct activation of TRPV4 channels by AA.
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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.