{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:54:04Z","timestamp":1787673244025,"version":"build-2736575974"},"reference-count":59,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:p>In liver cirrhosis, the altered levels of vasoactive substances, especially endothelin-1 (ET-1) and nitric oxide (NO) lead to elevated intrahepatic resistance, increased portal-systemic collaterals and abnormal intra- and extra-hepatic vascular responsiveness. These derangements aggravate portal hypertension-related complications such as gastro-oesophageal variceal bleeding. Homocysteine, a substance implicated in cardiovascular diseases, has been found with influences on vasoresponsiveness and angiogenesis. However, their relevant effects in liver cirrhosis have not been investigated. In the present study, liver cirrhosis was induced by common bile duct ligation (BDL) in Sprague\u2013Dawley rats. In acute study, the results showed that homocysteine enhanced hepatic vasoconstriction to ET-1 but decreased portal-systemic collateral vasocontractility to arginine vasopressin (AVP). Homocysteine down-regulated hepatic phosphorylated endothelial NO synthase (p-eNOS) and p-Akt protein expressions. Inducible NOS (iNOS) and cyclooxygenase (COX)-2 expressions were up-regulated by homocysteine in splenorenal shunt (SRS), the most prominent intra-abdominal collateral vessel. In chronic study, BDL or thioacetamide (TAA) rats received homocysteine or vehicle for 14\u00a0days. The results revealed that homocysteine increased hepatic collagen fibre deposition and fibrotic factors expressions in both BDL- and TAA-induced liver fibrotic rats. Portal-systemic shunting and expressions of mesenteric angiogenetic factors [vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), PDGF receptor \u03b2 (PDGFR\u03b2) and p-eNOS] were also increased in BDL rats. In conclusion, homocysteine is harmful to vascular derangements and liver fibrosis in cirrhosis.<\/jats:p>","DOI":"10.1042\/cs20160470","type":"journal-article","created":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T01:34:35Z","timestamp":1478050475000},"page":"69-86","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Homocysteine deteriorates intrahepatic derangement and portal-systemic collaterals in cirrhotic rats"],"prefix":"10.1042","volume":"131","author":[{"given":"Hung-Chun","family":"Tung","sequence":"first","affiliation":[{"name":"Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Jung","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan"},{"name":"Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Chang Gung University College of Medicine and Division of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Te-Yueh","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Fang","family":"Hsin","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan"},{"name":"Division of Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan"},{"name":"Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Te-Ia","family":"Huo","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fa-Yauh","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan"},{"name":"Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Chun","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan"},{"name":"Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan"},{"name":"Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Ling","family":"Ho","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan"},{"name":"Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shou-Dong","family":"Lee","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan"},{"name":"Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,12,9]]},"reference":[{"key":"2021113010504211400_B1","doi-asserted-by":"publisher","first-page":"S131","DOI":"10.1097\/01.mcg.0000155513.17715.f7","article-title":"Increased hepatic resistance: a new target in the pharmacologic therapy of portal hypertension","volume":"39","author":"Hernandez-Guerra","year":"2005","journal-title":"J. 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