{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:46:28Z","timestamp":1791773188714,"version":"4.3.4"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T00:00:00Z","timestamp":1493683200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T00:00:00Z","timestamp":1493683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>\n                    In cirrhosis, increased intrahepatic vascular resistance (IHVR) is the primary factor for portal hypertension (PH) development. Hepatic stellate cells (HSCs) play a major role increasing IHVR because, when activated, they are contractile and promote fibrogenesis. Protease\u2010activated receptors (PARs) can activate HSCs through thrombin and factor Xa, which are known PAR agonists, and cause microthrombosis in liver microcirculation. This study investigates the effects of the oral anticoagulant, rivaroxaban (RVXB), a direct antifactor Xa, on HSC phenotype, liver fibrosis (LF), liver microthrombosis, and PH in cirrhotic rats. Hepatic and systemic hemodynamic, nitric oxide (NO) bioavailability, LF, HSC activation, and microthrombosis were evaluated in CCl\n                    <jats:sub>4<\/jats:sub>\n                    and thioacetamide\u2010cirrhotic rats treated with RVXB (20 mg\/kg\/day) or its vehicle for 2 weeks. RVXB significantly decreased portal pressure (PP) in both models of cirrhosis without changes in portal blood flow, suggesting a reduction in IHVR. RVXB reduced oxidative stress, improved NO bioavailability, and ameliorated endothelial dysfunction. Rivaroxaban deactivated HSC, with decreased alpha\u2010smooth muscle actin and mRNA expression of other HSC activation markers. Despite this marked improvement in HSC phenotype, no significant changes in LF were identified. RVXB markedly reduced fibrin deposition, suggesting reduced intrahepatic microthrombosis.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : RVXB decreases PP in two rat models of cirrhosis. This effect is mostly associated with decreased IHVR, enhanced NO bioavailability, HSC deactivation, and reduced intrahepatic microthrombosis. Our findings suggest that RVXB deserves further evaluation as a potential treatment for cirrhotic PH. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2017;65:2031\u20102044).\n                  <\/jats:p>","DOI":"10.1002\/hep.29084","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T18:24:34Z","timestamp":1485887074000},"page":"2031-2044","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":107,"title":["The anticoagulant rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells"],"prefix":"10.1097","volume":"65","author":[{"given":"Marina","family":"Vilaseca","sequence":"first","affiliation":[{"name":"Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Cl\u00ednic, Barcelona, Spain,Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS),Spain"},{"name":"University of Barcelona Medical School,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"Garc\u00eda\u2010Calder\u00f3","sequence":"additional","affiliation":[{"name":"Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Cl\u00ednic, Barcelona, Spain,Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS),Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD),Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Lafoz","sequence":"additional","affiliation":[{"name":"Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Cl\u00ednic, Barcelona, Spain,Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS),Spain"},{"name":"University of Barcelona Medical School,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oihane","family":"Garc\u00eda\u2010Irigoyen","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD),Spain"},{"name":"Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA),Division of Hepatology; University of Navarra, IDISNA (Instituto de Investigacion Sanitaria de Navarra),Pamplona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat\u00edas A.","family":"Avila","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD),Spain"},{"name":"Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA),Division of Hepatology; University of Navarra, IDISNA (Instituto de Investigacion Sanitaria de Navarra),Pamplona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan Carles","family":"Reverter","sequence":"additional","affiliation":[{"name":"Hemotherapy and Hemostasis Department,Hospital Cl\u00ednic,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume","family":"Bosch","sequence":"additional","affiliation":[{"name":"Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Cl\u00ednic, Barcelona, Spain,Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS),Spain"},{"name":"University of Barcelona Medical School,Barcelona,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD),Spain"},{"name":"Swiss Liver Centre, Inselspital,Bern University,Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Hern\u00e1ndez\u2010Gea","sequence":"additional","affiliation":[{"name":"Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Cl\u00ednic, Barcelona, Spain,Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS),Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD),Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-4089","authenticated-orcid":false,"given":"Jordi","family":"Gracia\u2010Sancho","sequence":"additional","affiliation":[{"name":"Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Cl\u00ednic, Barcelona, Spain,Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS),Spain"},{"name":"University of Barcelona Medical School,Barcelona,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD),Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan Carles","family":"Garc\u00eda\u2010Pag\u00e1n","sequence":"additional","affiliation":[{"name":"Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Cl\u00ednic, Barcelona, Spain,Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS),Spain"},{"name":"University of Barcelona Medical School,Barcelona,Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD),Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,5,2]]},"reference":[{"issue":"1 Suppl","key":"hep29084-bib-0001-20241017","first-page":"141","article-title":"Complications of cirrhosis. 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