{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T11:59:06Z","timestamp":1782215946222,"version":"3.54.5"},"reference-count":44,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T00:00:00Z","timestamp":1656720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 109-2314-B-010-030"],"award-info":[{"award-number":["MOST 109-2314-B-010-030"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["111025"],"award-info":[{"award-number":["111025"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["111026"],"award-info":[{"award-number":["111026"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Szu-Zuan Research Foundation of Internal Medicine","award":["MOST 109-2314-B-010-030"],"award-info":[{"award-number":["MOST 109-2314-B-010-030"]}]},{"name":"Szu-Zuan Research Foundation of Internal Medicine","award":["111025"],"award-info":[{"award-number":["111025"]}]},{"name":"Szu-Zuan Research Foundation of Internal Medicine","award":["111026"],"award-info":[{"award-number":["111026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hyperlipidemia and oxidative stress with elevated oxidized low-density lipoprotein (ox-LDL) exacerbate hepatic inflammation and fibrosis. The plasma level of low-density lipoprotein (LDL) is controlled by proprotein convertase subtilisin\/kexin 9 (PCSK9). Alirocumab is a monoclonal antibody that decreases LDL via inhibiting PCSK9 function. Apart from lipid-lowering effects, alirocumab exerts anti-inflammation, anti-angiogenesis and anti-oxidant effects. This study aims to investigate the impact of alirocumab treatment on common bile duct ligation (BDL)-induced biliary cirrhotic rats. After a 4-week treatment of alirocumab, the hemodynamic data, blood biochemistry, ox-LDL level, oxidative stress markers, severity of hepatic encephalopathy and abnormal angiogenesis of BDL rats were measured and compared to the control group. BDL rats presented cirrhotic pictures and elevated ammonia, total cholesterol, LDL and ox-LDL levels compared to the control group. Alirocumab decreased plasma levels of total cholesterol, LDL, and oxidative stress markers; however, it did not affect the hemodynamics, liver and renal biochemistry, and the plasma levels of ammonia and ox-LDL. The motor activities, portal-systemic collaterals and mesenteric vascular density were not significantly different between alirocumab-treated and control groups. In addition, it did not affect hepatic inflammation, intrahepatic angiogenesis, liver fibrosis and free cholesterol accumulation in the liver of BDL rats. In conclusion, PCSK9 inhibition by alirocumab treatment ameliorates hyperlipidemia and systemic oxidative stress in biliary cirrhotic rats. However, it does not affect the plasma level of ox-LDL, intrahepatic inflammation and fibrosis. In addition, PCSK9 inhibition has a neutral effect on abnormal angiogenesis and hepatic encephalopathy in biliary cirrhotic rats.<\/jats:p>","DOI":"10.3390\/ijms23137378","type":"journal-article","created":{"date-parts":[[2022,7,3]],"date-time":"2022-07-03T22:50:46Z","timestamp":1656888646000},"page":"7378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effects of PCSK-9 Inhibition by Alirocumab Treatments on Biliary Cirrhotic Rats"],"prefix":"10.3390","volume":"23","author":[{"given":"Hui-Chun","family":"Huang","sequence":"first","affiliation":[{"name":"Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan"},{"name":"Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4884-634X","authenticated-orcid":false,"given":"Shao-Jung","family":"Hsu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-5389","authenticated-orcid":false,"given":"Ching-Chih","family":"Chang","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan"},{"name":"Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiao-Lin","family":"Chuang","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan"},{"name":"Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chih","family":"Hou","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fa-Yauh","family":"Lee","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cld.2013.12.001","article-title":"Pathophysiology of portal hypertension","volume":"18","author":"Iwakiri","year":"2014","journal-title":"Clin. 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