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–Dawley 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 days. 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 β (PDGFRβ) and p-eNOS] were also increased in BDL rats. In conclusion, homocysteine is harmful to vascular derangements and liver fibrosis in cirrhosis.
Skip Nav Destination
Article navigation
January 2017
-
Cover Image
Cover Image
Masson staining of rat liver specimens. Please see pp. 159-168 for more information. Image provided by Xujiong Li.
Research Article|
December 09 2016
Homocysteine deteriorates intrahepatic derangement and portal-systemic collaterals in cirrhotic rats
Hung-Chun Tung;
Hung-Chun Tung
1
*Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
Search for other works by this author on:
Shao-Jung Hsu;
Shao-Jung Hsu
1
*Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
†Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
‖Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
Search for other works by this author on:
Ming-Hung Tsai;
Ming-Hung Tsai
‡Chang Gung University College of Medicine and Division of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
Search for other works by this author on:
Te-Yueh Lin;
Te-Yueh Lin
†Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Search for other works by this author on:
I-Fang Hsin;
I-Fang Hsin
*Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
§Division of Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
‖Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
Search for other works by this author on:
Te-Ia Huo;
Te-Ia Huo
*Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
†Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Search for other works by this author on:
Fa-Yauh Lee;
†Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
‖Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
Correspondence: Dr Hui-Chun Huang (email [email protected]; [email protected]) or Dr Fa-Yauh Lee (email [email protected])
Search for other works by this author on:
Hui-Chun Huang;
†Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
‖Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
¶Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Correspondence: Dr Hui-Chun Huang (email [email protected]; [email protected]) or Dr Fa-Yauh Lee (email [email protected])
Search for other works by this author on:
Hsin-Ling Ho;
Hsin-Ling Ho
*Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
†Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Search for other works by this author on:
Han-Chieh Lin;
Han-Chieh Lin
†Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
‖Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
Search for other works by this author on:
Shou-Dong Lee
Shou-Dong Lee
‖Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
**Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
June 21 2016
Revision Received:
October 20 2016
Accepted:
November 01 2016
Accepted Manuscript online:
November 01 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2017) 131 (1): 69–86.
Article history
Received:
June 21 2016
Revision Received:
October 20 2016
Accepted:
November 01 2016
Accepted Manuscript online:
November 01 2016
Citation
Hung-Chun Tung, Shao-Jung Hsu, Ming-Hung Tsai, Te-Yueh Lin, I-Fang Hsin, Te-Ia Huo, Fa-Yauh Lee, Hui-Chun Huang, Hsin-Ling Ho, Han-Chieh Lin, Shou-Dong Lee; Homocysteine deteriorates intrahepatic derangement and portal-systemic collaterals in cirrhotic rats. Clin Sci (Lond) 1 January 2017; 131 (1): 69–86. doi: https://doi.org/10.1042/CS20160470
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |