{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:11:13Z","timestamp":1793254273559,"version":"4.5.0"},"reference-count":74,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/17\/11\/33042"],"award-info":[{"award-number":["RG\/17\/11\/33042"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["110044\/Z\/15\/Z"],"award-info":[{"award-number":["110044\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>PIEZO1 and TRPV4 are mechanically and osmotically regulated calcium\u2010permeable channels. The aim of this study was to determine the relevance and relationship of these channels in the contractile tone of the hepatic portal vein, which experiences mechanical and osmotic variations as it delivers blood to the liver from the intestines, gallbladder, pancreas and spleen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Wall tension was measured in freshly dissected portal veins from adult male mice, which were genetically unmodified or modified for either a non\u2010disruptive tag in native PIEZO1 or endothelial\u2010specific PIEZO1 deletion. Pharmacological agents were used to activate or inhibit PIEZO1, TRPV4 and associated pathways, including Yoda1 and Yoda2 for PIEZO1 and GSK1016790A for TRPV4 agonism, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PIEZO1 activation leads to nitric oxide synthase\u2010 and endothelium\u2010dependent relaxation of the portal vein. TRPV4 activation causes contraction, which is also endothelium\u2010dependent but independent of nitric oxide synthase. The TRPV4\u2010mediated contraction is suppressed by inhibitors of phospholipase A\n                      <jats:sub>2<\/jats:sub>\n                      and cyclooxygenases and mimicked by prostaglandin E\n                      <jats:sub>2<\/jats:sub>\n                      , suggesting mediation by arachidonic acid metabolism. TRPV4 antagonism inhibits the effect of agonising TRPV4 but not PIEZO1. Increased wall stretch and hypo\u2010osmolality inhibit TRPV4 responses while lacking effects on or amplifying PIEZO1 responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The portal vein contains independently functioning PIEZO1 channels and TRPV4 channels in the endothelium, the pharmacological activation of which leads to opposing effects of vessel relaxation (PIEZO1) and contraction (TRPV4). In mechanical and osmotic strain, the PIEZO1 mechanism dominates. Modulators of these channels could present important new opportunities for manipulating liver perfusion and regeneration in disease and surgical procedures.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15646","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T18:52:32Z","timestamp":1687632752000},"page":"2026-2038","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Independent endothelial functions of\n                    <scp>PIEZO1<\/scp>\n                    and\n                    <scp>TRPV4<\/scp>\n                    in hepatic portal vein and predominance of\n                    <scp>PIEZO1<\/scp>\n                    in mechanical and osmotic stress"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5014-7666","authenticated-orcid":false,"given":"Naima","family":"Endesh","sequence":"first","affiliation":[{"name":"School of Medicine University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0767-6877","authenticated-orcid":false,"given":"Eulashini","family":"Chuntharpursat\u2010Bon","sequence":"additional","affiliation":[{"name":"School of Medicine University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Revill","sequence":"additional","affiliation":[{"name":"School of Chemistry University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6213-6358","authenticated-orcid":false,"given":"Nadira Y.","family":"Yuldasheva","sequence":"additional","affiliation":[{"name":"School of Medicine University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3810-190X","authenticated-orcid":false,"given":"T. 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