{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:08:31Z","timestamp":1790755711519,"version":"4.1.0"},"reference-count":89,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"National Research Agency (ANR)","doi-asserted-by":"publisher","award":["ANR-16-RHUS-0003"],"award-info":[{"award-number":["ANR-16-RHUS-0003"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"National Research Agency (ANR)","doi-asserted-by":"publisher","award":["GSC G4"],"award-info":[{"award-number":["GSC G4"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FHU CARNAVAL project","award":["ANR-16-RHUS-0003"],"award-info":[{"award-number":["ANR-16-RHUS-0003"]}]},{"name":"FHU CARNAVAL project","award":["GSC G4"],"award-info":[{"award-number":["GSC G4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The role of ion channels is extensively described in the context of the electrical activity of excitable cells and in excitation-contraction coupling. They are, through this phenomenon, a key element for cardiac activity and its dysfunction. They also participate in cardiac morphological remodeling, in particular in situations of hypertrophy. Alongside this, a new field of exploration concerns the role of ion channels in valve development and remodeling. Cardiac valves are important components in the coordinated functioning of the heart by ensuring unidirectional circulation essential to the good efficiency of the cardiac pump. In this review, we will focus on the ion channels involved in both the development and\/or the pathological remodeling of the aortic valve. Regarding valve development, mutations in genes encoding for several ion channels have been observed in patients suffering from malformation, including the bicuspid aortic valve. Ion channels were also reported to be involved in the morphological remodeling of the valve, characterized by the development of fibrosis and calcification of the leaflets leading to aortic stenosis. The final stage of aortic stenosis requires, until now, the replacement of the valve. Thus, understanding the role of ion channels in the progression of aortic stenosis is an essential step in designing new therapeutic approaches in order to avoid valve replacement.<\/jats:p>","DOI":"10.3390\/ijms24065860","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T04:33:31Z","timestamp":1679286811000},"page":"5860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ion Channels in the Development and Remodeling of the Aortic Valve"],"prefix":"10.3390","volume":"24","author":[{"given":"Christophe","family":"Simard","sequence":"first","affiliation":[{"name":"UR 4650, Physiopathologie et Strat\u00e9gies d\u2019Imagerie du Remodelage Cardiovasculaire, GIP Cyceron, Unicaen, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaux","family":"Aize","sequence":"additional","affiliation":[{"name":"UR 4650, Physiopathologie et Strat\u00e9gies d\u2019Imagerie du Remodelage Cardiovasculaire, GIP Cyceron, Unicaen, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Chaigne","sequence":"additional","affiliation":[{"name":"IHU LIRYC Electrophysiology and Heart Modeling Institute, Foundation Bordeaux, 33600 Pessac, France"},{"name":"Electrophysiology and Ablation Unit, Bordeaux University Hospital, 33600 Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlyne","family":"Mpweme Bangando","sequence":"additional","affiliation":[{"name":"UR 4650, Physiopathologie et Strat\u00e9gies d\u2019Imagerie du Remodelage Cardiovasculaire, GIP Cyceron, Unicaen, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Guinamard","sequence":"additional","affiliation":[{"name":"UR 4650, Physiopathologie et Strat\u00e9gies d\u2019Imagerie du Remodelage Cardiovasculaire, GIP Cyceron, Unicaen, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1136\/heart.83.1.81","article-title":"Clinical significance of the bicuspid aortic valve","volume":"83","author":"Ward","year":"2000","journal-title":"Heart"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0195-668X(03)00201-X","article-title":"A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease","volume":"24","author":"Iung","year":"2003","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.jacc.2007.06.024","article-title":"Insights into degenerative aortic valve disease","volume":"50","author":"Goldbarg","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1136\/heartjnl-2015-308765","article-title":"Radiation-induced valvular heart disease","volume":"102","author":"Gujral","year":"2016","journal-title":"Heart"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00392-021-01809-y","article-title":"Pathomechanisms and therapeutic opportunities in radiation-induced heart disease: From bench to bedside","volume":"110","author":"Varga","year":"2021","journal-title":"Clin. Res. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1161\/CIRCULATIONAHA.119.041080","article-title":"Contemporary Presentation and Management of Valvular Heart Disease: The EURObservational Research Programme Valvular Heart Disease II Survey","volume":"140","author":"Iung","year":"2019","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0140-6736(06)69208-8","article-title":"Burden of valvular heart diseases: A population-based study","volume":"368","author":"Nkomo","year":"2006","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev-physiol-012110-142145","article-title":"Heart valve structure and function in development and disease","volume":"73","author":"Hinton","year":"2011","journal-title":"Annu. Rev. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e006339","DOI":"10.1161\/JAHA.117.006339","article-title":"Valve Interstitial Cells: The Key to Understanding the Pathophysiology of Heart Valve Calcification","volume":"6","author":"Rutkovskiy","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Feulner, L., van Vliet, P.P., Puceat, M., and Andelfinger, G. (2022). Endocardial Regulation of Cardiac Development. J. Cardiovasc. Dev. Dis., 9.","DOI":"10.3390\/jcdd9050122"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"783543","DOI":"10.3389\/fcvm.2022.783543","article-title":"Uncoupling the Vicious Cycle of Mechanical Stress and Inflammation in Calcific Aortic Valve Disease","volume":"9","author":"Dayawansa","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"851945","DOI":"10.1155\/2015\/851945","article-title":"Innate and Adaptive Immunity in Calcific Aortic Valve Disease","volume":"2015","author":"Mathieu","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1080\/19768354.2018.1528175","article-title":"Involvement of inflammatory responses in the early development of calcific aortic valve disease: Lessons from statin therapy","volume":"22","author":"Lee","year":"2018","journal-title":"Anim. Cells. Syst. (Seoul)"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1161\/CIRCGENETICS.115.001145","article-title":"Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease","volume":"8","author":"Droit","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1161\/ATVBAHA.120.314789","article-title":"Cell-Type Transcriptome Atlas of Human Aortic Valves Reveal Cell Heterogeneity and Endothelial to Mesenchymal Transition Involved in Calcific Aortic Valve Disease","volume":"40","author":"Xu","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5867","DOI":"10.1111\/febs.15665","article-title":"TRPV4 integrates matrix mechanosensing with Ca2+ signaling to regulate extracellular matrix remodeling","volume":"288","author":"Ji","year":"2021","journal-title":"FEBS J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/d41586-021-01283-6","article-title":"Medecine Nobel for duo who discovered biology of sense","volume":"598","author":"LedFord","year":"2021","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/gb-2011-12-3-218","article-title":"The transient receptor potential family of ion channels","volume":"12","author":"Nilius","year":"2011","journal-title":"Genome Biol."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1152\/physrev.00026.2014","article-title":"Transient receptor potential channels in the vasculature","volume":"95","author":"Earley","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1111\/bph.13392","article-title":"What is the evidence for the role of TRP channels in inflammatory and immune cells?","volume":"173","author":"Parenti","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"jcs238360","DOI":"10.1242\/jcs.238360","article-title":"Mammalian TRP ion channels are insensitive to membrane stretch","volume":"132","author":"Nikolaev","year":"2019","journal-title":"J. Cell. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/nature10812","article-title":"Piezo proteins are pore-forming subunits of mechanically activated channels","volume":"483","author":"Coste","year":"2012","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13578-020-00522-z","article-title":"Structure, kinetic properties and biological function of mechanosensitive Piezo channels","volume":"11","author":"Fang","year":"2021","journal-title":"Cell Biosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1016\/j.neuron.2022.07.001","article-title":"PIEZO channels and newcomers in the mammalian mechanosensitive ion channel family","volume":"110","author":"Delmas","year":"2022","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature25453","article-title":"Structure of the mechanically activated ion channel Piezo1","volume":"554","author":"Saotome","year":"2018","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nature25743","article-title":"Structure and mechanogating mechanism of the Piezo1 channel","volume":"554","author":"Zhao","year":"2018","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1111\/febs.14711","article-title":"The mechanosensitive Piezo1 channel: A three-bladed propeller-like structure and a lever-like mechanogating mechanism","volume":"286","author":"Zhao","year":"2019","journal-title":"FEBS J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.yjmcc.2020.03.013","article-title":"Piezo1 is required for outflow tract and aortic valve development","volume":"143","author":"Faucherre","year":"2020","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e44706","DOI":"10.7554\/eLife.44706","article-title":"Mechanically activated piezo channels modulate outflow tract valve development through the Yap1 and Klf2-Notch signaling axis","volume":"8","author":"Duchemin","year":"2019","journal-title":"Elife"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mpweme Bangando, H., Simard, C., Aize, M., Lebrun, A., Manrique, A., Guinamard, R., and On Behalf Of The Stop-As Investigators (2022). TRPM4 Participates in Irradiation-Induced Aortic Valve Remodeling in Mice. Cancers, 14.","DOI":"10.3390\/cancers14184477"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/j.cub.2015.03.038","article-title":"Oscillatory Flow Modulates Mechanosensitive klf2a Expression through trpv4 and trpp2 during Heart Valve Development","volume":"25","author":"Heckel","year":"2015","journal-title":"Curr. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1086\/342360","article-title":"KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes","volume":"71","author":"Andelfinger","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.nmd.2020.07.001","article-title":"Cardiac MRI identifies valvular and myocardial disease in a subset of ANO5-related muscular dystrophy patients","volume":"30","author":"Srinivasan","year":"2020","journal-title":"Neuromuscul. Disord."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"766416","DOI":"10.3389\/fphar.2021.766416","article-title":"Loss-of-Function Piezo1 Mutations Display Altered Stability Driven by Ubiquitination and Proteasomal Degradation","volume":"12","author":"Zhou","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12817","DOI":"10.1073\/pnas.1817070115","article-title":"Mechanically activated ion channel PIEZO1 is required for lymphatic valve formation","volume":"115","author":"Nonomura","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","first-page":"e1","article-title":"Endocardial Notch Signaling in Cardiac Development and Disease","volume":"118","author":"MacGrogan","year":"2016","journal-title":"Circ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/dvdy.401","article-title":"Emerging role of Piezo ion channels in cardiovascular development","volume":"251","author":"Shah","year":"2022","journal-title":"Dev. Dyn."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1101\/gad.276304","article-title":"Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation","volume":"18","author":"Timmerman","year":"2004","journal-title":"Genes Dev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nature03940","article-title":"Mutations in NOTCH1 cause aortic valve disease","volume":"437","author":"Garg","year":"2005","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1002\/dvdy.22391","article-title":"Adam10 is essential for early embryonic cardiovascular development","volume":"239","author":"Zhang","year":"2010","journal-title":"Dev. Dyn."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1161\/CIRCRESAHA.115.307738","article-title":"ADAM10-Dependent Signaling Through Notch1 and Notch4 Controls Development of Organ-Specific Vascular Beds","volume":"119","author":"Alabi","year":"2016","journal-title":"Circ. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1152\/physrev.00029.2017","article-title":"Intriguing Roles for Endothelial ADAM10\/Notch Signaling in the Development of Organ-Specific Vascular Beds","volume":"98","author":"Alabi","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e50684","DOI":"10.7554\/eLife.50684","article-title":"Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells","volume":"9","author":"Caolo","year":"2020","journal-title":"Elife"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"731101","DOI":"10.3389\/fcell.2021.731101","article-title":"Strong as a Hippo\u2019s Heart: Biomechanical Hippo Signaling During Zebrafish Cardiac Development","volume":"9","author":"Bornhorst","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"27176","DOI":"10.1074\/jbc.M110.143370","article-title":"Wild-type and brachyolmia-causing mutant TRPV4 channels respond directly to stretch force","volume":"285","author":"Loukin","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.yjmcc.2013.01.019","article-title":"The TRPM4 non-selective cation channel contributes to the mammalian atrial action potential","volume":"59","author":"Simard","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1177\/0300985819900018","article-title":"Bicuspid Aortic Valve in 2 Model Species and Review of the Literature","volume":"57","year":"2020","journal-title":"Vet. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1172\/JCI38292","article-title":"Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I","volume":"119","author":"Kruse","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_52","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_53","doi-asserted-by":"crossref","unstructured":"Liu, H., Chatel, S., Simard, C., Syam, N., Salle, L., Probst, V., Morel, J., Millat, G., Lopez, M., and Abriel, H. (2013). Molecular genetics and functional anomalies in a series of 248 Brugada cases with 11 mutations in the TRPM4 channel. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054131"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1016\/j.gendis.2022.01.001","article-title":"ANO5-related muscle diseases: From clinics and genetics to pathology and research strategies","volume":"9","author":"Christiansen","year":"2022","journal-title":"Genes Dis."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Al-Shammari, H., Latif, N., Sarathchandra, P., McCormack, A., Rog-Zielinska, E.A., Raja, S., Kohl, P., Yacoub, M.H., Peyronnet, R., and Chester, A.H. (2020). Expression and function of mechanosensitive ion channels in human valve interstitial cells. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240532"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e22306","DOI":"10.1096\/fj.202101863R","article-title":"Hydrogel cultures reveal Transient Receptor Potential Vanilloid 4 regulation of myofibroblast activation and proliferation in valvular interstitial cells","volume":"36","author":"Batan","year":"2022","journal-title":"FASEB J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e2000268","DOI":"10.1002\/mabi.202000268","article-title":"Calcium Signaling Regulates Valvular Interstitial Cell Alignment and Myofibroblast Activation in Fast-Relaxing Boronate Hydrogels","volume":"20","author":"Ma","year":"2020","journal-title":"Macromol. Biosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e155569","DOI":"10.1172\/jci.insight.155569","article-title":"Increased Ca2+ influx through CaV1.2 drives aortic valve calcification","volume":"7","author":"Matsui","year":"2022","journal-title":"JCI Insight."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"19336","DOI":"10.1073\/pnas.1306369110","article-title":"Hydrogels preserve native phenotypes of valvular fibroblasts through an elasticity-regulated PI3K\/AKT pathway","volume":"110","author":"Wang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.devcel.2012.08.017","article-title":"A TRPC6-dependent pathway for myofibroblast transdifferentiation and wound healing in vivo","volume":"23","author":"Davis","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1007\/s00424-020-02476-0","article-title":"TRPM4 non-selective cation channel in human atrial fibroblast growth","volume":"472","author":"Simard","year":"2020","journal-title":"Pflugers Arch."},{"key":"ref_62","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_63","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_64","doi-asserted-by":"crossref","first-page":"e66582","DOI":"10.7554\/eLife.66582","article-title":"The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy","volume":"10","author":"Guo","year":"2021","journal-title":"Elife"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s44161-022-00082-0","article-title":"Piezo1 is the cardiac mechanosensor that initiates the cardiomyocyte hypertrophic response to pressure overload in adult mice","volume":"1","author":"Yu","year":"2022","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1039\/c0ib00034e","article-title":"Ultra-rapid activation of TRPV4 ion channels by mechanical forces applied to cell surface beta1 integrins","volume":"2","author":"Matthews","year":"2010","journal-title":"Integr. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wang, X., Ali, M.S., and Lacerda, C.M.R. (2018). A Three-Dimensional Collagen-Elastin Scaffold for Heart Valve Tissue Engineering. Bioengineering, 5.","DOI":"10.3390\/bioengineering5030069"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"968393","DOI":"10.3389\/fphys.2022.968393","article-title":"Emerging role of transient receptor potential (TRP) ion channels in cardiac fibroblast pathophysiology","volume":"13","author":"Gwanyanya","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1152\/physiolgenomics.00041.2016","article-title":"RNA expression profile of calcified bicuspid, tricuspid, and normal human aortic valves by RNA sequencing","volume":"48","author":"Droit","year":"2016","journal-title":"Physiol. Genom."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"101015","DOI":"10.1016\/j.jbc.2021.101015","article-title":"TRPM4 links calcium signaling to membrane potential in pancreatic acinar cells","volume":"297","author":"Magyar","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1152\/physiol.00007.2016","article-title":"Ion Channels in Endothelial Responses to Fluid Shear Stress","volume":"31","author":"Gerhold","year":"2016","journal-title":"Physiology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1161\/01.RES.0000255691.76142.4a","article-title":"Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms","volume":"100","author":"Aird","year":"2007","journal-title":"Circ. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1161\/01.ATV.0000196624.70507.0d","article-title":"Transcriptional profiles of valvular and vascular endothelial cells reveal phenotypic differences: Influence of shear stress","volume":"26","author":"Butcher","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Hsu, C.D., Tchir, A., Mirza, A., Chaparro, D., Herrera, R.E., Hutcheson, J.D., and Ramaswamy, S. (2022). Valve Endothelial Cell Exposure to High Levels of Flow Oscillations Exacerbates Valve Interstitial Cell Calcification. Bioengineering, 9.","DOI":"10.3390\/bioengineering9080393"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"H15","DOI":"10.1152\/ajpheart.00228.2013","article-title":"Side-specific mechanical properties of valve endothelial cells","volume":"307","author":"Miragoli","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1016\/j.ajpath.2013.01.037","article-title":"Side-specific endothelial-dependent regulation of aortic valve calcification: Interplay of hemodynamics and nitric oxide signaling","volume":"182","author":"Richards","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nature13701","article-title":"Piezo1 integration of vascular architecture with physiological force","volume":"515","author":"Li","year":"2014","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"17587","DOI":"10.1074\/jbc.M117.810325","article-title":"Molecular and functional characterization of the endothelial ATP-sensitive potassium channel","volume":"292","author":"Aziz","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"765419","DOI":"10.3389\/fcvm.2021.765419","article-title":"Pathogenesis and Molecular Immune Mechanism of Calcified Aortic Valve Disease","volume":"8","author":"Bian","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1126\/science.1098845","article-title":"TRPM4 regulates calcium oscillations after T cell activation","volume":"306","author":"Launay","year":"2004","journal-title":"Science"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1038\/ni.1648","article-title":"The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells","volume":"9","author":"Barbet","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.4049\/jimmunol.1102969","article-title":"The TRPM4 channel controls monocyte and macrophage, but not neutrophil, function for survival in sepsis","volume":"189","author":"Serafini","year":"2012","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"828115","DOI":"10.3389\/fimmu.2021.828115","article-title":"Diverse Roles of TRPV4 in Macrophages: A Need for Unbiased Profiling","volume":"12","author":"Nguyen","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1038\/s41467-021-23482-5","article-title":"Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing","volume":"12","author":"Atcha","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1161\/CIRCULATIONAHA.120.045536","article-title":"Transcatheter Aortic Valve Implantation Represents an Anti-Inflammatory Therapy Via Reduction of Shear Stress-Induced, Piezo-1-Mediated Monocyte Activation","volume":"142","author":"Baratchi","year":"2020","journal-title":"Circulation"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s13578-022-00929-w","article-title":"Mechanosensitive piezo1 calcium channel activates connexin 43 hemichannels through PI3K signaling pathway in bone","volume":"12","author":"Zeng","year":"2022","journal-title":"Cell Biosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"174113","DOI":"10.1016\/j.ejphar.2021.174113","article-title":"Activation of transient receptor potential vanilloid channel 4 contributes to the development of ethanol-induced gastric injury in mice","volume":"902","author":"Pacheco","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Cs\u00edp\u0151, T., Czikora, \u00c1., F\u00fcl\u00f6p, G.\u00c1., Guly\u00e1s, H., Rutkai, I., T\u00f3th, E.P., P\u00f3rsz\u00e1sz, R., Szalai, A., B\u00f6lcskei, K., and Helyes, Z. (2022). A Central Role for TRPM4 in Ca2+-Signal Amplification and Vasoconstriction. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031465"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fphar.2016.00121","article-title":"Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery","volume":"7","author":"Imbrici","year":"2016","journal-title":"Front. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5860\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:59:01Z","timestamp":1760122741000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,20]]},"references-count":89,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065860"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065860","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,20]]}}}