{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:00:49Z","timestamp":1791388849460,"version":"4.3.3"},"reference-count":184,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T00:00:00Z","timestamp":1686960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Agency","award":["ANR-10-IAHU-04"],"award-info":[{"award-number":["ANR-10-IAHU-04"]}]},{"name":"National Research Agency","award":["19-CE44-0010-02"],"award-info":[{"award-number":["19-CE44-0010-02"]}]},{"name":"National Research Agency","award":["AAPR2020I-2019-8151810"],"award-info":[{"award-number":["AAPR2020I-2019-8151810"]}]},{"name":"National Research Agency","award":["18CE14002701"],"award-info":[{"award-number":["18CE14002701"]}]},{"name":"French ANR CANALBRET","award":["ANR-10-IAHU-04"],"award-info":[{"award-number":["ANR-10-IAHU-04"]}]},{"name":"French ANR CANALBRET","award":["19-CE44-0010-02"],"award-info":[{"award-number":["19-CE44-0010-02"]}]},{"name":"French ANR CANALBRET","award":["AAPR2020I-2019-8151810"],"award-info":[{"award-number":["AAPR2020I-2019-8151810"]}]},{"name":"French ANR CANALBRET","award":["18CE14002701"],"award-info":[{"award-number":["18CE14002701"]}]},{"name":"New Aquitaine regional council PHYSTRIG","award":["ANR-10-IAHU-04"],"award-info":[{"award-number":["ANR-10-IAHU-04"]}]},{"name":"New Aquitaine regional council PHYSTRIG","award":["19-CE44-0010-02"],"award-info":[{"award-number":["19-CE44-0010-02"]}]},{"name":"New Aquitaine regional council PHYSTRIG","award":["AAPR2020I-2019-8151810"],"award-info":[{"award-number":["AAPR2020I-2019-8151810"]}]},{"name":"New Aquitaine regional council PHYSTRIG","award":["18CE14002701"],"award-info":[{"award-number":["18CE14002701"]}]},{"name":"ANR MEGAVOLT","award":["ANR-10-IAHU-04"],"award-info":[{"award-number":["ANR-10-IAHU-04"]}]},{"name":"ANR MEGAVOLT","award":["19-CE44-0010-02"],"award-info":[{"award-number":["19-CE44-0010-02"]}]},{"name":"ANR MEGAVOLT","award":["AAPR2020I-2019-8151810"],"award-info":[{"award-number":["AAPR2020I-2019-8151810"]}]},{"name":"ANR MEGAVOLT","award":["18CE14002701"],"award-info":[{"award-number":["18CE14002701"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The transient receptor potential vanilloid 4 (TRPV4) channel is a non-selective cation channel that is mostly permeable to calcium (Ca2+), which participates in intracellular Ca2+ handling in cardiac cells. It is widely expressed through the body and is activated by a large spectrum of physicochemical stimuli, conferring it a role in a variety of sensorial and physiological functions. Within the cardiovascular system, TRPV4 expression is reported in cardiomyocytes, endothelial cells (ECs) and smooth muscle cells (SMCs), where it modulates mitochondrial activity, Ca2+ homeostasis, cardiomyocytes electrical activity and contractility, cardiac embryonic development and fibroblast proliferation, as well as vascular permeability, dilatation and constriction. On the other hand, TRPV4 channels participate in several cardiac pathological processes such as the development of cardiac fibrosis, hypertrophy, ischemia\u2013reperfusion injuries, heart failure, myocardial infarction and arrhythmia. In this manuscript, we provide an overview of TRPV4 channel implications in cardiac physiology and discuss the potential of the TRPV4 channel as a therapeutic target against cardiovascular diseases.<\/jats:p>","DOI":"10.3390\/cells12121654","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T01:31:14Z","timestamp":1687138274000},"page":"1654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Pathophysiological Roles of the TRPV4 Channel in the Heart"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7141-8469","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Chaigne","sequence":"first","affiliation":[{"name":"IHU LIRYC Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Universit\u00e9, 33600 Bordeaux, France"},{"name":"Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM U1045, University of Bordeaux, 33600 Pessac, France"},{"name":"Electrophysiology and Ablation Unit, Bordeaux University Hospital, 33604 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol\u00e8ne","family":"Barbeau","sequence":"additional","affiliation":[{"name":"Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM U1045, University of Bordeaux, 33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5146-6869","authenticated-orcid":false,"given":"Thomas","family":"Ducret","sequence":"additional","affiliation":[{"name":"Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM U1045, University of Bordeaux, 33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Guinamard","sequence":"additional","affiliation":[{"name":"UR4650, Physiopathologie et Strat\u00e9gies d\u2019Imagerie du Remodelage Cardiovasculaire, GIP Cyceron, Universit\u00e9 de Caen Normandie, 14032 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7159-3451","authenticated-orcid":false,"given":"David","family":"Benoist","sequence":"additional","affiliation":[{"name":"IHU LIRYC Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Universit\u00e9, 33600 Bordeaux, France"},{"name":"Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM U1045, University of Bordeaux, 33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.conb.2004.05.003","article-title":"TRP ion channels in the nervous system","volume":"14","author":"Moran","year":"2004","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1146\/annurev-pharmtox-010617-052832","article-title":"TRP Channels as Potential Drug Targets","volume":"58","author":"Moran","year":"2018","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/s41569-018-0145-2","article-title":"Transient receptor potential channels in cardiac health and disease","volume":"16","author":"Hof","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1152\/physrev.00016.2015","article-title":"TRPV4: Molecular Conductor of a Diverse Orchestra","volume":"96","author":"White","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"734113","DOI":"10.3389\/fphys.2021.734113","article-title":"Role of Known Transient Receptor Potential Vanilloid Channels in Modulating Cardiac Mechanobiology","volume":"12","author":"Miller","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s00395-015-0512-7","article-title":"TRPV4 channels: Physiological and pathological role in cardiovascular system","volume":"110","author":"Randhawa","year":"2015","journal-title":"Basic Res. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.semcdb.2018.11.002","article-title":"TRP channels in cardiac and intestinal fibrosis","volume":"94","author":"Inoue","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"H1156","DOI":"10.1152\/ajpheart.00497.2020","article-title":"Transient receptor potential vanilloid 4 channel participates in mouse ventricular electrical activity","volume":"320","author":"Chaigne","year":"2021","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"244","DOI":"10.2174\/1573403X15666190307112326","article-title":"Physiological and Pathological Role of TRPV1, TRPV2 and TRPV4 Channels in Heart","volume":"15","author":"Gorbunov","year":"2019","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.4081\/ejh.2012.e32","article-title":"Unusual localization and translocation of TRPV4 protein in cultured ventricular myocytes of the neonatal rat","volume":"56","author":"Zhao","year":"2012","journal-title":"Eur. J. Histochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1093\/cvr\/cvy156","article-title":"TRPV4 increases cardiomyocyte calcium cycling and contractility yet contributes to damage in the aged heart following hypoosmotic stress","volume":"115","author":"Jones","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1074\/jbc.M511456200","article-title":"Human TRPV4 channel splice variants revealed a key role of ankyrin domains in multimerization and trafficking","volume":"281","author":"Arniges","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11210","DOI":"10.1074\/jbc.M109.090712","article-title":"A 3.5-nm structure of rat TRPV4 cation channel revealed by Zernike phase-contrast cryoelectron microscopy","volume":"285","author":"Shigematsu","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6195","DOI":"10.1021\/bi300279b","article-title":"Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel","volume":"51","author":"Inada","year":"2012","journal-title":"Biochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4994","DOI":"10.1038\/ncomms5994","article-title":"TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P(2)","volume":"5","author":"Takahashi","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/s41594-018-0037-5","article-title":"Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms","volume":"25","author":"Deng","year":"2018","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/embor.2012.219","article-title":"The puzzle of TRPV4 channelopathies","volume":"14","author":"Nilius","year":"2013","journal-title":"EMBO Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1242\/jcs.01675","article-title":"Homo- and heteromeric assembly of TRPV channel subunits","volume":"118","author":"Hellwig","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"25006","DOI":"10.1074\/jbc.C600153200","article-title":"Structure of the N-terminal ankyrin repeat domain of the TRPV2 ion channel","volume":"281","author":"Jin","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature12822","article-title":"Structure of the TRPV1 ion channel determined by electron cryo-microscopy","volume":"504","author":"Liao","year":"2013","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.neuron.2007.05.027","article-title":"The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity","volume":"54","author":"Lishko","year":"2007","journal-title":"Neuron"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1110\/ps.062357206","article-title":"Crystal structure of the human TRPV2 channel ankyrin repeat domain","volume":"15","author":"McCleverty","year":"2006","journal-title":"Protein Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6272","DOI":"10.1074\/jbc.M706386200","article-title":"Stimulus-specific modulation of the cation channel TRPV4 by PACSIN 3","volume":"283","author":"Owsianik","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"36561","DOI":"10.1074\/jbc.M703903200","article-title":"OS-9 regulates the transit and polyubiquitination of TRPV4 in the endoplasmic reticulum","volume":"282","author":"Wang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1080\/19336950.2018.1438009","article-title":"Sensing and regulation of cell volume\u2014We know so much and yet understand so little: TRPV4 as a sensor of volume changes but possibly without a volume-regulatory role?","volume":"12","author":"Larsen","year":"2018","journal-title":"Channels"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"26541","DOI":"10.1074\/jbc.M302590200","article-title":"Plant, Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a C-terminal calmodulin binding site","volume":"278","author":"Strotmann","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9400","DOI":"10.1073\/pnas.1510602112","article-title":"A channelopathy mechanism revealed by direct calmodulin activation of TrpV4","volume":"112","author":"Loukin","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"51448","DOI":"10.1074\/jbc.M308212200","article-title":"Microtubule-associated [corrected] protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4)","volume":"278","author":"Suzuki","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.bpj.2010.05.012","article-title":"Atomic force microscopy reveals the alternating subunit arrangement of the TRPP2-TRPV4 heterotetramer","volume":"99","author":"Stewart","year":"2010","journal-title":"Biophys. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.ceca.2011.08.006","article-title":"Heteromeric TRPV4-C1 channels contribute to store-operated Ca(2+) entry in vascular endothelial cells","volume":"50","author":"Ma","year":"2011","journal-title":"Cell Calcium"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4677","DOI":"10.1096\/fj.14-251652","article-title":"TRPV4, TRPC1, and TRPP2 assemble to form a flow-sensitive heteromeric channel","volume":"28","author":"Du","year":"2014","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1073\/pnas.1012867108","article-title":"An aquaporin-4\/transient receptor potential vanilloid 4 (AQP4\/TRPV4) complex is essential for cell-volume control in astrocytes","volume":"108","author":"Benfenati","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15485","DOI":"10.1074\/jbc.M600549200","article-title":"A role for AQP5 in activation of TRPV4 by hypotonicity: Concerted involvement of AQP5 and TRPV4 in regulation of cell volume recovery","volume":"281","author":"Liu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jcb.23382","article-title":"Functional interaction between AQP2 and TRPV4 in renal cells","volume":"113","author":"Galizia","year":"2012","journal-title":"J. Cell. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Verkerk, A.O., Lodder, E.M., and Wilders, R. (2019). Aquaporin Channels in the Heart-Physiology and Pathophysiology. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20082039"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/1874091X01509010024","article-title":"Phosphorylation on TRPV4 Serine 824 Regulates Interaction with STIM1","volume":"9","author":"Shin","year":"2015","journal-title":"Open Biochem. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"30115","DOI":"10.1074\/jbc.M110.141549","article-title":"Arresting a transient receptor potential (TRP) channel: Beta-arrestin 1 mediates ubiquitination and functional down-regulation of TRPV4","volume":"285","author":"Shukla","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1016\/j.bbamem.2011.07.049","article-title":"Electrophysiological properties of heteromeric TRPV4-C1 channels","volume":"1808","author":"Ma","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1083\/jcb.200805124","article-title":"TRPP2 and TRPV4 form a polymodal sensory channel complex","volume":"182","author":"Buchholz","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/978-94-007-0265-3_28","article-title":"Voltage sensing in thermo-TRP channels","volume":"Volume 704","author":"Brauchi","year":"2011","journal-title":"Transient Receptor Potential Channels"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1126\/science.1116270","article-title":"Voltage sensor of Kv1.2: Structural basis of electromechanical coupling","volume":"309","author":"Long","year":"2005","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1126\/science.1116269","article-title":"Crystal structure of a mammalian voltage-dependent Shaker family K+ channel","volume":"309","author":"Long","year":"2005","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1126\/science.aaf8070","article-title":"Structure of the voltage-gated K(+) channel Eag1 reveals an alternative voltage sensing mechanism","volume":"353","author":"Whicher","year":"2016","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cell.2016.12.023","article-title":"Structures of the Human HCN1 Hyperpolarization-Activated Channel","volume":"168","author":"Lee","year":"2017","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"47044","DOI":"10.1074\/jbc.M208277200","article-title":"Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells","volume":"277","author":"Watanabe","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"33704","DOI":"10.1074\/jbc.M204828200","article-title":"Molecular determinants of permeation through the cation channel TRPV4","volume":"277","author":"Voets","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"C195","DOI":"10.1152\/ajpcell.00365.2003","article-title":"TRPV4 calcium entry channel: A paradigm for gating diversity","volume":"286","author":"Nilius","year":"2004","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1080\/13543776.2021.1903432","article-title":"TRPV4 antagonists: A patent review (2015\u20132020)","volume":"31","author":"Lawhorn","year":"2021","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/BF02125730","article-title":"Channel-mediated calcium current in the heart","volume":"1","author":"Coetzee","year":"1988","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/415198a","article-title":"Cardiac excitation-contraction coupling","volume":"415","author":"Bers","year":"2002","journal-title":"Nature"},{"key":"ref_51","first-page":"e137528","article-title":"TRPV4 blockade suppresses atrial fibrillation in sterile pericarditis rats","volume":"5","author":"Liao","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s40256-018-00320-6","article-title":"Clinical Pharmacokinetics, Safety, and Tolerability of a Novel, First-in-Class TRPV4 Ion Channel Inhibitor, GSK2798745, in Healthy and Heart Failure Subjects","volume":"19","author":"Goyal","year":"2019","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"127022","DOI":"10.1016\/j.bmcl.2020.127022","article-title":"Recent advances in TRPV4 agonists and antagonists","volume":"30","author":"Lawhorn","year":"2020","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1152\/physrev.00019.2017","article-title":"Properties of the TRPV4 Activator GSK1016790A and the TRPV4 Antagonist GSK2193874","volume":"97","author":"Thorneloe","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2828","DOI":"10.1038\/cddis.2017.227","article-title":"Activation of transient receptor potential vanilloid 4 involves in hypoxia\/reoxygenation injury in cardiomyocytes","volume":"8","author":"Wu","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fphar.2019.00006","article-title":"The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels","volume":"10","author":"Baratchi","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"677661","DOI":"10.3389\/fmolb.2021.677661","article-title":"Role of Transient Receptor Potential Vanilloid 4 in Vascular Function","volume":"8","author":"Liu","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1021\/acs.jmedchem.8b01615","article-title":"Discovery of Novel Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists as Regulators of Chondrogenic Differentiation: Identification of Quinazolin-4(3 H)-ones and in Vivo Studies on a Surgically Induced Rat Model of Osteoarthritis","volume":"62","author":"Atobe","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.pharmthera.2017.02.019","article-title":"Modulation of the TRPV4 ion channel as a therapeutic target for disease","volume":"177","author":"Grace","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.bbrc.2009.09.007","article-title":"Identification and characterization of novel TRPV4 modulators","volume":"389","author":"Vincent","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"42678","DOI":"10.1038\/srep42678","article-title":"Blockage of transient receptor potential vanilloid 4 alleviates myocardial ischemia\/reperfusion injury in mice","volume":"7","author":"Dong","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1021\/ml300449k","article-title":"Optimization of a Novel Series of TRPV4 Antagonists with In Vivo Activity in a Model of Pulmonary Edema","volume":"4","author":"Hilfiker","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4011","DOI":"10.1016\/j.bmcl.2015.06.098","article-title":"Identification of orally-bioavailable antagonists of the TRPV4 ion-channel","volume":"25","author":"Wei","year":"2015","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9270","DOI":"10.1021\/acs.jmedchem.9b01247","article-title":"Discovery of GSK3527497: A Candidate for the Inhibition of Transient Receptor Potential Vanilloid-4 (TRPV4)","volume":"62","author":"Brooks","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1016\/j.bmcl.2016.09.013","article-title":"Discovery of novel 2\u2019,4\u2019-dimethyl-[4,5\u2019-bithiazol]-2-yl amino derivatives as orally bioavailable TRPV4 antagonists for the treatment of pain: Part 1","volume":"26","author":"Tsuno","year":"2016","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4936","DOI":"10.1016\/j.bmcl.2016.09.014","article-title":"Discovery of novel 2\u2019,4\u2019-dimethyl-[4,5\u2019-bithiazol]-2-yl amino derivatives as orally bioavailable TRPV4 antagonists for the treatment of pain: Part 2","volume":"26","author":"Tsuno","year":"2016","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11209","DOI":"10.1021\/acs.jmedchem.8b01344","article-title":"Design and Optimization of Sulfone Pyrrolidine Sulfonamide Antagonists of Transient Receptor Potential Vanilloid-4 with in Vivo Activity in a Pulmonary Edema Model","volume":"61","author":"Pero","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/sj.bjp.0705443","article-title":"Protein kinase C-mediated Ca2+ entry in HEK 293 cells transiently expressing human TRPV4","volume":"140","author":"Xu","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_69","unstructured":"Duncton, M. (2015). TRP Channels as Therapeutic Targets, Academic Press."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1111\/j.1476-5381.2012.02186.x","article-title":"4alpha-phorbol 12,13-didecanoate activates cultured mouse dorsal root ganglia neurons independently of TRPV4","volume":"168","author":"Alexander","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"L824","DOI":"10.1152\/ajplung.00244.2011","article-title":"Implication of the ryanodine receptor in TRPV4-induced calcium response in pulmonary arterial smooth muscle cells from normoxic and chronically hypoxic rats","volume":"303","author":"Dahan","year":"2012","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/nature01807","article-title":"Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels","volume":"424","author":"Watanabe","year":"2003","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.yjmcc.2009.02.028","article-title":"Epoxyeicosatrienoic acids limit damage to mitochondrial function following stress in cardiac cells","volume":"46","author":"Katragadda","year":"2009","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"642470","DOI":"10.3389\/fphys.2021.642470","article-title":"The Role of Epoxyeicosatrienoic Acids in Cardiac Remodeling","volume":"12","author":"Lai","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/bcp.12603","article-title":"The role of epoxyeicosatrienoic acids in the cardiovascular system","volume":"80","author":"Yang","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"159ra148","DOI":"10.1126\/scitranslmed.3004276","article-title":"An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure","volume":"4","author":"Thorneloe","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"37622","DOI":"10.18632\/oncotarget.9376","article-title":"A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis","volume":"7","author":"Xu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"H33","DOI":"10.1152\/ajpheart.00303.2013","article-title":"Analysis of responses to the TRPV4 agonist GSK1016790A in the pulmonary vascular bed of the intact-chest rat","volume":"306","author":"Pankey","year":"2014","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"102483","DOI":"10.1016\/j.ceca.2021.102483","article-title":"Activation of transient receptor potential vanilloid 4 exacerbates myocardial ischemia-reperfusion injury via JNK-CaMKII phosphorylation pathway in isolated mice hearts","volume":"100","author":"Zhang","year":"2021","journal-title":"Cell Calcium"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1124\/jpet.107.134551","article-title":"Systemic activation of the transient receptor potential vanilloid subtype 4 channel causes endothelial failure and circulatory collapse: Part 2","volume":"326","author":"Willette","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.yjmcc.2012.10.016","article-title":"TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals","volume":"54","author":"Adapala","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"162","DOI":"10.5603\/CJ.a2019.0050","article-title":"Transient receptor potential channel TRPV4 mediates TGF-beta1-induced differentiation of human ventricular fibroblasts","volume":"27","author":"Ahn","year":"2020","journal-title":"Cardiol. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1111\/bph.15267","article-title":"Structural determinants of TRPV4 inhibition and identification of new antagonists with antiviral activity","volume":"179","author":"Duarte","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/FJC.0b013e318279ba42","article-title":"TRPV4 and the regulation of vascular tone","volume":"61","author":"Filosa","year":"2013","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.vph.2017.08.005","article-title":"Heteromeric TRPV4\/TRPC1 channels mediate calcium-sensing receptor-induced nitric oxide production and vasorelaxation in rabbit mesenteric arteries","volume":"96\u201398","author":"Greenberg","year":"2017","journal-title":"Vasc. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1016\/j.bbadis.2017.07.021","article-title":"An abnormal TRPV4-related cytosolic Ca(2+) rise in response to uniaxial stretch in induced pluripotent stem cells-derived cardiomyocytes from dilated cardiomyopathy patients","volume":"1863","author":"Lu","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA) -Mol. Basis Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"C704","DOI":"10.1152\/ajpcell.00099.2013","article-title":"TRPV4 channel contributes to serotonin-induced pulmonary vasoconstriction and the enhanced vascular reactivity in chronic hypoxic pulmonary hypertension","volume":"305","author":"Xia","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3453","DOI":"10.1172\/JCI31766","article-title":"Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding","volume":"117","author":"Gevaert","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/apha.12477","article-title":"TRPV4 activates autonomic and behavioural warmth-defence responses in Wistar rats","volume":"214","author":"Vizin","year":"2015","journal-title":"Acta Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1007\/s12012-020-09572-8","article-title":"TRPV4 Mediates Cardiac Fibrosis via the TGF-beta1\/Smad3 Signaling Pathway in Diabetic Rats","volume":"20","author":"Jia","year":"2020","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"382a","DOI":"10.1016\/j.bpj.2018.11.2074","article-title":"TRPV4 Contributes to Stretch-Induced Hypercontractility and Time-Dependent Dysfunction in the Aged Heart","volume":"116","author":"Veteto","year":"2019","journal-title":"Biophys. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1021\/acsmedchemlett.7b00094","article-title":"Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4","volume":"8","author":"Cheung","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"20220129","DOI":"10.1098\/rsbl.2022.0129","article-title":"Systemic application of the transient receptor potential vanilloid-type 4 antagonist GSK2193874 induces tail vasodilation in a mouse model of thermoregulation","volume":"18","author":"Staunton","year":"2022","journal-title":"Biol. Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1021\/acsmedchemlett.1c00406","article-title":"Identification, Synthesis, and Characterization of a Major Circulating Human Metabolite of TRPV4 Antagonist GSK2798745","volume":"12","author":"Pero","year":"2021","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"9738","DOI":"10.1021\/acs.jmedchem.8b01317","article-title":"Discovery of Pyrrolidine Sulfonamides as Selective and Orally Bioavailable Antagonists of Transient Receptor Potential Vanilloid-4 (TRPV4)","volume":"61","author":"Brnardic","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"22664","DOI":"10.1074\/jbc.M302561200","article-title":"Impaired pressure sensation in mice lacking TRPV4","volume":"278","author":"Suzuki","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"13698","DOI":"10.1073\/pnas.1735416100","article-title":"Abnormal osmotic regulation in trpv4-\/- mice","volume":"100","author":"Liedtke","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1161\/HYPERTENSIONAHA.108.127100","article-title":"Transient receptor potential vanilloid type 4-deficient mice exhibit impaired endothelium-dependent relaxation induced by acetylcholine in vitro and in vivo","volume":"53","author":"Zhang","year":"2009","journal-title":"Hypertension"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1161\/01.RES.0000187474.47805.30","article-title":"Modulation of the Ca2 permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium","volume":"97","author":"Vriens","year":"2005","journal-title":"Circ. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"H466","DOI":"10.1152\/ajpheart.00854.2009","article-title":"TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress","volume":"298","author":"Mendoza","year":"2010","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1126\/science.1216283","article-title":"Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function","volume":"336","author":"Sonkusare","year":"2012","journal-title":"Science"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"H1096","DOI":"10.1152\/ajpheart.00241.2009","article-title":"TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure","volume":"297","author":"Earley","year":"2009","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/cvr\/cvn207","article-title":"Role of cytochrome P450-dependent transient receptor potential V4 activation in flow-induced vasodilatation","volume":"80","author":"Loot","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Hartmannsgruber, V., Heyken, W.-T., Kacik, M., Kaistha, A., Grgic, I., Harteneck, C., Liedtke, W., Hoyer, J., and Kohler, R. (2007). Arterial response to shear stress critically depends on endothelial TRPV4 expression. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000827"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"C96","DOI":"10.1152\/ajpcell.00559.2002","article-title":"Impaired osmotic sensation in mice lacking TRPV4","volume":"285","author":"Mizuno","year":"2003","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.neulet.2005.03.035","article-title":"Hearing impairment in TRPV4 knockout mice","volume":"382","author":"Tabuchi","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1161\/01.RES.0000247065.11756.19","article-title":"Transient receptor potential vanilloid 4-mediated disruption of the alveolar septal barrier: A novel mechanism of acute lung injury","volume":"99","author":"Alvarez","year":"2006","journal-title":"Circ. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"F667","DOI":"10.1152\/ajprenal.00458.2005","article-title":"TRPV4 as a flow sensor in flow-dependent K+ secretion from the cortical collecting duct","volume":"292","author":"Taniguchi","year":"2007","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"eabc6967","DOI":"10.1126\/scisignal.abc6967","article-title":"Mechanical activation of TRPV4 channels controls albumin reabsorption by proximal tubule cells","volume":"13","author":"Gualdani","year":"2020","journal-title":"Sci. Signal."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.cmet.2008.08.002","article-title":"TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts","volume":"8","author":"Masuyama","year":"2008","journal-title":"Cell Metab."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"7327","DOI":"10.1113\/JP273595","article-title":"TRPV4 participates in pressure-induced inhibition of renin secretion by juxtaglomerular cells","volume":"594","author":"Seghers","year":"2016","journal-title":"J. Physiol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Kunert-Keil, C., Bisping, F., Kr\u00fcger, J., and Brinkmeier, H. (2006). Tissue-specific expression of TRP channel genes in the mouse and its variation in three different mouse strains. BMC Genom., 7.","DOI":"10.1186\/1471-2164-7-159"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1093\/cvr\/cvz287","article-title":"Transient receptor potential vanilloid-4 contributes to stretch-induced hypercontractility and time-dependent dysfunction in the aged heart","volume":"116","author":"Veteto","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.yjmcc.2015.08.005","article-title":"Uniaxial cyclic stretch stimulates TRPV4 to induce realignment of human embryonic stem cell-derived cardiomyocytes","volume":"87","author":"Qi","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"211","DOI":"10.4161\/chan.24328","article-title":"TRP to cardiac fibroblast differentiation","volume":"7","author":"Thodeti","year":"2013","journal-title":"Channels"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.lfs.2009.10.013","article-title":"Cardiac fibroblasts have functional TRPV4 activated by 4alpha-phorbol 12,13-didecanoate","volume":"85","author":"Hatano","year":"2009","journal-title":"Life Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1161\/CIRCRESAHA.109.206771","article-title":"TRPM7-mediated Ca2+ signals confer fibrogenesis in human atrial fibrillation","volume":"106","author":"Du","year":"2010","journal-title":"Circ. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1161\/01.ATV.0000225698.36212.6a","article-title":"Evidence for a functional role of endothelial transient receptor potential V4 in shear stress-induced vasodilatation","volume":"26","author":"Heyken","year":"2006","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1124\/mol.112.078584","article-title":"Optical recording reveals novel properties of GSK1016790A-induced vanilloid transient receptor potential channel TRPV4 activity in primary human endothelial cells","volume":"82","author":"Sullivan","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.phrs.2013.09.005","article-title":"TRPV4 channel activation leads to endothelium-dependent relaxation mediated by nitric oxide and endothelium-derived hyperpolarizing factor in rat pulmonary artery","volume":"78","author":"Sukumaran","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"H634","DOI":"10.1152\/ajpheart.00717.2011","article-title":"Activation of endothelial TRPV4 channels mediates flow-induced dilation in human coronary arterioles: Role of Ca2+ entry and mitochondrial ROS signaling","volume":"302","author":"Bubolz","year":"2012","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"L555","DOI":"10.1152\/ajplung.00005.2011","article-title":"Upregulation of osmo-mechanosensitive TRPV4 channel facilitates chronic hypoxia-induced myogenic tone and pulmonary hypertension","volume":"302","author":"Yang","year":"2012","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00424-015-1704-6","article-title":"Effect of hypoxia on TRPV1 and TRPV4 channels in rat pulmonary arterial smooth muscle cells","volume":"468","author":"Parpaite","year":"2016","journal-title":"Pflug. Arch."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1748-1716.2010.02217.x","article-title":"TRPV channels and vascular function","volume":"203","author":"Baylie","year":"2011","journal-title":"Acta Physiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1113\/JP279570","article-title":"Mechanisms underlying selective coupling of endothelial Ca(2+) signals with eNOS vs. IK\/SK channels in systemic and pulmonary arteries","volume":"598","author":"Ottolini","year":"2020","journal-title":"J. Physiol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ceca.2007.05.018","article-title":"Serotonin-induced activation of TRPV4-like current in rat intrapulmonary arterial smooth muscle cells","volume":"43","author":"Ducret","year":"2008","journal-title":"Cell Calcium"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"C373","DOI":"10.1152\/ajpcell.00115.2014","article-title":"Flow shear stress enhances intracellular Ca2+ signaling in pulmonary artery smooth muscle cells from patients with pulmonary arterial hypertension","volume":"307","author":"Song","year":"2014","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Barbeau, S., Gilbert, G., Cardouat, G., Baudrimont, I., Freund-Michel, V., Guibert, C., Marthan, R., Vacher, P., Quignard, J.-F., and Ducret, T. (2021). Mechanosensitivity in Pulmonary Circulation: Pathophysiological Relevance of Stretch-Activated Channels in Pulmonary Hypertension. Biomolecules, 11.","DOI":"10.3390\/biom11091389"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/cvr\/cvv022","article-title":"TRPC3 contributes to regulation of cardiac contractility and arrhythmogenesis by dynamic interaction with NCX1","volume":"106","author":"Doleschal","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ijcard.2015.10.018","article-title":"TRPC3 regulates the automaticity of embryonic stem cell-derived cardiomyocytes","volume":"203","author":"Qi","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/cvr\/cvv213","article-title":"TRPM4 in cardiac electrical activity","volume":"108","author":"Guinamard","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1113\/JP271347","article-title":"TRPM4 non-selective cation channels influence action potentials in rabbit Purkinje fibres","volume":"594","author":"Hof","year":"2016","journal-title":"J. Physiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1016\/j.hrthm.2013.08.014","article-title":"Implication of the TRPM4 nonselective cation channel in mammalian sinus rhythm","volume":"10","author":"Hof","year":"2013","journal-title":"Hear. Rhythm."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"E3037","DOI":"10.1073\/pnas.1311865110","article-title":"Ion channel-kinase TRPM7 is required for maintaining cardiac automaticity","volume":"110","author":"Sah","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e002103","DOI":"10.1161\/CIRCGEN.118.002103","article-title":"TRPM4 Mutation in Patients With Ventricular Noncompaction and Cardiac Conduction Disease","volume":"11","author":"Saito","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3389\/fphys.2018.00177","article-title":"Four TRPM4 Cation Channel Mutations Found in Cardiac Conduction Diseases Lead to Altered Protein Stability","volume":"9","author":"Bianchi","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1161\/CIRCGENETICS.109.930867","article-title":"Gain-of-function mutations in TRPM4 cause autosomal dominant isolated cardiac conduction disease","volume":"3","author":"Liu","year":"2010","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/humu.21599","article-title":"Mutational spectrum in the Ca(2+)\u2014Activated cation channel gene TRPM4 in patients with cardiac conductance disturbances","volume":"33","author":"Stallmeyer","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Palladino, A., Papa, A.A., Petillo, R., Scutifero, M., Morra, S., Passamano, L., Nigro, V., and Politano, L. (2022). The Role of TRPM4 Gene Mutations in Causing Familial Progressive Cardiac Conduction Disease: A Further Contribution. Genes, 13.","DOI":"10.3390\/genes13020258"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Demion, M., Thireau, J., Gueffier, M., Finan, A., Khoueiry, Z., Cassan, C., Serafini, N., Aimond, F., Granier, M., and Pasqui\u00e9, J.-L. (2014). Trpm4 gene invalidation leads to cardiac hypertrophy and electrophysiological alterations. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115256"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Jin, M., Wu, Z., Chen, L., Jaimes, J., Collins, D., Walters, E.T., and O\u2019Neil, R.G. (2011). Determinants of TRPV4 activity following selective activation by small molecule agonist GSK1016790A. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016713"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1161\/CIRCRESAHA.117.310230","article-title":"Calcium and Excitation-Contraction Coupling in the Heart","volume":"121","author":"Eisner","year":"2017","journal-title":"Circ. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s10741-016-9571-6","article-title":"Cardiac contractility modulation: A novel approach for the treatment of heart failure","volume":"21","author":"Gutterman","year":"2016","journal-title":"Hear. Fail. Rev."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3389\/fcvm.2019.00083","article-title":"TRP Channels Mediated Pathological Ca2+-Handling and Spontaneous Ectopy","volume":"6","author":"Ezeani","year":"2019","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Emir, T.L.R. (2017). Neurobiology of TRP Channels, CRC Press.","DOI":"10.4324\/9781315152837"},{"key":"ref_146","first-page":"181","article-title":"Role of transient receptor potential vanilloid 4 in the effect of osmotic pressure on myocardial contractility in rat","volume":"60","author":"Li","year":"2008","journal-title":"Sheng Li Xue Bao Acta Physiol. Sin."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"7283683","DOI":"10.1155\/2019\/7283683","article-title":"Blockade of Transient Receptor Potential Vanilloid 4 Enhances Antioxidation after Myocardial Ischemia\/Reperfusion","volume":"2019","author":"Wu","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_148","first-page":"3","article-title":"Preservation of Cardiac Function and Attenuation of Remodelling in Transient Receptor Potential Vanilloid 4 Knockout Mice Following Myocardial Infarction","volume":"6","author":"Turner","year":"2015","journal-title":"Clin. Exp. Cardiol."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Rosenbaum, T., Ben\u00edtez-Angeles, M., S\u00e1nchez-Hern\u00e1ndez, R., Morales-L\u00e1zaro, S.L., Hiriart, M., Morales-Buenrostro, L.E., and Torres-Quiroz, F. (2020). TRPV4: A Physio and Pathophysiologically Significant Ion Channel. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113837"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/bs.ctm.2020.01.007","article-title":"Endothelial TRPV4 channels and vasodilator reactivity","volume":"85","author":"Chen","year":"2020","journal-title":"Curr. Top Membr."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Barbeau, S., Joushomme, A., Chappe, Y., Cardouat, G., Baudrimont, I., Freund-Michel, V., Guibert, C., Marthan, R., Berger, P., and Vacher, P. (2022). Cell Confluence Modulates TRPV4 Channel Activity in Response to Hypoxia. Biomolecules, 12.","DOI":"10.3390\/biom12070954"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1161\/01.RES.0000194321.60300.d6","article-title":"TRPV4 forms a novel Ca2+ signaling complex with ryanodine receptors and BKCa channels","volume":"97","author":"Earley","year":"2005","journal-title":"Circ. Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"L893","DOI":"10.1152\/ajplung.00430.2017","article-title":"Reactive oxygen species induced Ca(2+) influx via TRPV4 and microvascular endothelial dysfunction in the SU5416\/hypoxia model of pulmonary arterial hypertension","volume":"314","author":"Suresh","year":"2018","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"100171","DOI":"10.1074\/jbc.RA120.015059","article-title":"Piezo1 acts upstream of TRPV4 to induce pathological changes in endothelial cells due to shear stress","volume":"296","author":"Swain","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/FJC.0000000000000714","article-title":"A Novel Mechanism of Sildenafil Improving the Excessive Proliferation and H2S Production in Pulmonary Arterial Smooth Muscle Cells","volume":"74","author":"Yao","year":"2019","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"100145","DOI":"10.1016\/j.jlr.2021.100145","article-title":"Membrane cholesterol regulates TRPV4 function, cytoskeletal expression, and the cellular response to tension","volume":"62","author":"Lakk","year":"2021","journal-title":"J. Lipid Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.carpath.2016.08.004","article-title":"Endoglin selectively modulates transient receptor potential channel expression in left and right heart failure","volume":"25","author":"Morine","year":"2016","journal-title":"Cardiovasc. Pathol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e74519","DOI":"10.7554\/eLife.74519","article-title":"Activation of transient receptor potential vanilloid 4 is involved in pressure overload-induced cardiac hypertrophy","volume":"11","author":"Zou","year":"2022","journal-title":"Elife"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1016\/S0140-6736(16)00620-6","article-title":"Clinical workload in UK primary care: A retrospective analysis of 100 million consultations in England, 2007-14","volume":"387","author":"Hobbs","year":"2016","journal-title":"Lancet"},{"key":"ref_160","first-page":"188","article-title":"Oral administration of TRPV4 inhibitor improves atrial calcium handling abnormalities in sterile pericarditis rats","volume":"74","author":"Liao","year":"2022","journal-title":"Sheng Li Xue Bao Acta Physiol. Sin."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1093\/cvr\/cvab141","article-title":"Arrhythmogenesis in the aged heart following ischaemia-reperfusion: Role of transient receptor potential vanilloid 4","volume":"118","author":"Peana","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.vph.2012.07.003","article-title":"The role of cardiac fibroblasts in the transition from inflammation to fibrosis following myocardial infarction","volume":"58","author":"Turner","year":"2013","journal-title":"Vascul. Pharmacol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1196\/annals.1380.007","article-title":"Dynamic interactions between myocytes, fibroblasts, and extracellular matrix","volume":"1080","author":"Banerjee","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.tcm.2017.01.011","article-title":"Myocardial fibrosis predicts ventricular tachyarrhythmias","volume":"27","author":"Disertori","year":"2017","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Adapala, R.K., Katari, V., Teegala, L.R., Thodeti, S., Paruchuri, S., and Thodeti, C.K. (2021). TRPV4 Mechanotransduction in Fibrosis. Cells, 10.","DOI":"10.3390\/cells10113053"},{"key":"ref_166","first-page":"158","article-title":"Aging and Cardiac Fibrosis","volume":"2","author":"Biernacka","year":"2011","journal-title":"Aging Dis."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/cvr\/cvaa324","article-title":"Cardiac fibrosis","volume":"117","author":"Frangogiannis","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s00395-020-0775-5","article-title":"TRPV4 deletion protects heart from myocardial infarction-induced adverse remodeling via modulation of cardiac fibroblast differentiation","volume":"115","author":"Adapala","year":"2020","journal-title":"Basic Res. Cardiol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"L135","DOI":"10.1152\/ajplung.00084.2019","article-title":"TRPV4 channel mediates adventitial fibroblast activation and adventitial remodeling in pulmonary hypertension","volume":"318","author":"Cussac","year":"2020","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1161\/01.RES.0000129579.59664.9d","article-title":"Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1","volume":"94","author":"Verheule","year":"2004","journal-title":"Circ. Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1161\/CIRCEP.109.931634","article-title":"Fibrillatory conduction in the atrial free walls of goats in persistent and permanent atrial fibrillation","volume":"3","author":"Verheule","year":"2010","journal-title":"Circ. Arrhythmia Electrophysiol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1253\/circj.CJ-11-1301","article-title":"Triggered firing and atrial fibrillation in transgenic mice with selective atrial fibrosis induced by overexpression of TGF-beta1","volume":"76","author":"Choi","year":"2012","journal-title":"Circ. J."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Verheule, S., and Schotten, U. (2021). Electrophysiological Consequences of Cardiac Fibrosis. Cells, 10.","DOI":"10.3390\/cells10113220"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/ng0210-98","article-title":"Channelopathies converge on TRPV4","volume":"42","author":"Nilius","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00424-010-0788-2","article-title":"Transient receptor potential channelopathies","volume":"460","author":"Nilius","year":"2010","journal-title":"Pflug. Arch."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"jcs258372","DOI":"10.1242\/jcs.258372","article-title":"TRP channels in health and disease at a glance","volume":"134","author":"Yue","year":"2021","journal-title":"J. Cell Sci."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/ng.508","article-title":"Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C","volume":"42","author":"Olschewski","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/ng.509","article-title":"Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4","volume":"42","author":"Deng","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10048-012-0328-7","article-title":"TRPV4 mutations in children with congenital distal spinal muscular atrophy","volume":"13","author":"Fiorillo","year":"2012","journal-title":"Neurogenetics"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/ng.945","article-title":"Mutations in TRPV4 cause an inherited arthropathy of hands and feet","volume":"43","author":"Yuan","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ng.512","article-title":"Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C","volume":"42","author":"Martinez","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Toft-Bertelsen, T.L., and MacAulay, N. (2021). TRPing to the Point of Clarity: Understanding the Function of the Complex TRPV4 Ion Channel. Cells, 10.","DOI":"10.3390\/cells10010165"},{"key":"ref_183","unstructured":"in, GeneReviews((R)), and Adam, M.P. (1993). Autosomal Dominant TRPV4 Disorders, University of Washington."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/acn3.51523","article-title":"TRPV4 mutations causing mixed neuropathy and skeletal phenotypes result in severe gain of function","volume":"9","author":"Taga","year":"2022","journal-title":"Ann. Clin. Transl. Neurol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/12\/1654\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:55:36Z","timestamp":1760126136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/12\/1654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,17]]},"references-count":184,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["cells12121654"],"URL":"https:\/\/doi.org\/10.3390\/cells12121654","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,17]]}}}