{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:08:23Z","timestamp":1777003703057,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,12,19]],"date-time":"2012-12-19T00:00:00Z","timestamp":1355875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>In cirrhosis, sinusoidal endothelial cell injury results in increased endothelin\u20101 (<jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101) and decreased nitric oxide synthase (<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>) activity, leading to portal hypertension. However, the effects of transplanted endothelial progenitor cells (<jats:styled-content style=\"fixed-case\">EPCs<\/jats:styled-content>) on the cirrhotic liver have not yet been clarified. We investigated whether <jats:styled-content style=\"fixed-case\">EPC<\/jats:styled-content> transplantation reduces portal hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cirrhotic rats were created by the administration of carbon tetrachloride (<jats:styled-content style=\"fixed-case\">CCl<\/jats:styled-content><jats:sub>4<\/jats:sub>) twice weekly for 10\u2009weeks. From week 7, rat bone marrow\u2010derived <jats:styled-content style=\"fixed-case\">EPCs<\/jats:styled-content> were injected via the tail vein in this model once a week for 4\u2009weeks. Endothelial <jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>), vascular endothelial growth factor (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>) and caveolin expressions were examined by <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>estern blots. Hepatic tissue <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 was measured by a radioimmunoassay (<jats:styled-content style=\"fixed-case\">RIA<\/jats:styled-content>). Portal venous pressure, mean aortic pressure, and hepatic blood flow were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Endothelial progenitor cell transplantation reduced liver fibrosis, \u03b1\u2010smooth muscle actin\u2010positive cells, caveolin expression, <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 concentration and portal venous pressure. <jats:styled-content style=\"fixed-case\">EPC<\/jats:styled-content> transplantation increased hepatic blood flow, protein levels of <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>. Immunohistochemical analyses of <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content> and isolectin <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>4 demonstrated that the livers of <jats:styled-content style=\"fixed-case\">EPC<\/jats:styled-content>\u2010transplanted animals had markedly increased vascular density, suggesting reconstitution of sinusoidal blood vessels with endothelium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Transplantation of <jats:styled-content style=\"fixed-case\">EPCs<\/jats:styled-content> ameliorates vascular dysfunction and portal hypertension, suggesting this treatment may provide a new approach in the therapy of portal hypertension with liver cirrhosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1440-1746.2012.07238.x","type":"journal-article","created":{"date-parts":[[2012,7,31]],"date-time":"2012-07-31T16:20:14Z","timestamp":1343751614000},"page":"168-178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Transplantation of endothelial progenitor cells ameliorates vascular dysfunction and portal hypertension in carbon tetrachloride\u2010induced rat liver cirrhotic model"],"prefix":"10.1111","volume":"28","author":[{"given":"Masaharu","family":"Sakamoto","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Medicine Faculty of Medicine Fukuoka University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine Kurume University School of Medicine  Kurume Japan"},{"name":"Liver Cancer 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