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We have shown that cirrhotic livers have increased reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>, our aim was to assess the effects of the oral mitochondria\u2010targeted antioxidant mitoquinone on hepatic oxidative stress, <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> phenotype, liver fibrosis and portal hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ex vivo: Hepatic stellate cells phenotype was analysed in human precision\u2010cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> phenotype, proliferation and viability were assessed in <jats:styled-content style=\"fixed-case\">LX<\/jats:styled-content>2, and in primary human and rat <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> treated with mitoquinone or vehicle. In vivo: <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>\u2010 and thioacetamide\u2010cirrhotic rats were treated with mitoquinone (5\u00a0mg\/kg\/day) or the vehicle compound, Decyl<jats:styled-content style=\"fixed-case\">TPP<\/jats:styled-content>, for 2\u00a0weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> phenotype and liver inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mitoquinone deactivated human and rat <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>, decreased their proliferation but with no effects on viability. In <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>\u2010cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide\u2010cirrhotic model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We propose mitochondria\u2010targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13436","type":"journal-article","created":{"date-parts":[[2017,4,4]],"date-time":"2017-04-04T23:27:36Z","timestamp":1491348456000},"page":"1002-1012","source":"Crossref","is-referenced-by-count":45,"title":["Mitochondria\u2010targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats"],"prefix":"10.1111","volume":"37","author":[{"given":"Marina","family":"Vilaseca","sequence":"first","affiliation":[{"name":"Barcelona Hepatic Hemodynamic Laboratory Liver Unit Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Hospital Cl\u00ednic de Barcelona University of Barcelona Medical 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