Liver cirrhosis is characterized by portal hypertension. However, the alteration of portal hypertension-related derangements during cirrhosis resolution is not well known. The present study aimed to establish animal models with cirrhosis resolution and to investigate the relevant changes during this process. Male Sprague–Dawley rats were applied. In reverse thioacetamide (rTAA) model, rats were randomly allocated into four groups with control, thioacetamide (TAA) cirrhosis and rTAA groups that discontinued TAA for 4 or 8 weeks after cirrhosis induction. In reverse bile duct ligation (rBDL) model, rats received choledochoduodenal shunt surgery upon the establishment of cirrhosis and 4, 8, or 16 weeks were allowed after the surgery. At the end, portal hypertension-related parameters were evaluated. Cirrhosis resolution was observed in rTAA groups. Portal pressure (PP) decreased after cirrhosis resolution but remained higher than control group (control, TAA, rTAA4, rTAA8 (mmHg): 5.4 ± 0.3, 12.9 ± 0.3, 8.6 ± 0.4, 7.6 ± 0.6). Further survey found the increased splanchnic blood flow did not reduce during cirrhosis resolution. The extrahepatic pathological angiogenesis was not ameliorated (% of mesenteric window area: 1.2 ± 0.3, 7.3 ± 1.1, 8.3 ± 1.0, 11.3 ± 2.7). In collateral system, the shunting degree reduced while the vessels structure remained. The vascular contractility of all systems and nitric oxide (NO) production were normalized. In rBDL series, PP decreased in rBDL16 groups but the extrahepatic angiogenesis persisted. In conclusion, cirrhosis resolution attenuates but not completely normalizes portal hypertension because of persistently high splanchnic inflow and angiogenesis. In clinical setting, vascular complications such as varices could persist after cirrhosis resolution and further investigation to define the follow-up and treatment strategies is anticipated.
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March 2018
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Cover Image
Cover Image
CD31 immunofluorescence staining of a mesenteric window taken from a rat with liver cirrhosis. In Clinical Science volume 132, Issue 6, Huang et al. use CD31 immunofluorescence staining to show an increased density of the vascular network in the mesenteric window of rats with bile duct ligation-induced liver cirrhosis. Vascular network density is usually low in non-cirrhotic condition, indicating that mesenteric angiogenesis takes place in liver cirrhosis; for details see pages 669–683.
Research Article|
March 26 2018
Extrahepatic angiogenesis hinders recovery of portal hypertension and collaterals in rats with cirrhosis resolution
Shao-Jung Hsu;
Shao-Jung Hsu
1Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
2Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Ming-Hung Tsai;
Ming-Hung Tsai
3Division of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Lin-Kuo Medical Center; Chang Gung University, College of Medicine, Taoyuan, Taiwan
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Ching-Chih Chang;
Ching-Chih Chang
1Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
4Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Yu-Hsin Hsieh;
Yu-Hsin Hsieh
2Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Hui-Chun Huang;
1Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
2Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
4Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Correspondence: Fa-Yauh Lee (fylee@vghtpe.gov.tw) or Hui-Chun Huang (hchuang2@vghtpe.gov.tw)
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Fa-Yauh Lee;
1Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
2Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Correspondence: Fa-Yauh Lee (fylee@vghtpe.gov.tw) or Hui-Chun Huang (hchuang2@vghtpe.gov.tw)
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Chiao-Ling Chuang;
Chiao-Ling Chuang
1Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
4Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Ming-Chih Hou;
Ming-Chih Hou
1Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
2Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Shou-Dong Lee
Shou-Dong Lee
1Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
5Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan
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Publisher: Portland Press Ltd
Received:
September 19 2017
Revision Received:
February 09 2018
Accepted:
February 15 2018
Accepted Manuscript online:
February 15 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (6): 669–683.
Article history
Received:
September 19 2017
Revision Received:
February 09 2018
Accepted:
February 15 2018
Accepted Manuscript online:
February 15 2018
Connected Content
A commentary has been published:
Cirrhosis regression: extrahepatic angiogenesis and liver hyperarterialization persist
See also
Citation
Shao-Jung Hsu, Ming-Hung Tsai, Ching-Chih Chang, Yu-Hsin Hsieh, Hui-Chun Huang, Fa-Yauh Lee, Chiao-Ling Chuang, Ming-Chih Hou, Shou-Dong Lee; Extrahepatic angiogenesis hinders recovery of portal hypertension and collaterals in rats with cirrhosis resolution. Clin Sci (Lond) 30 March 2018; 132 (6): 669–683. doi: https://doi.org/10.1042/CS20171370
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