Folic acid ameliorates homocysteine-induced angiogenesis and portosystemic collaterals in cirrhotic rats

Hsin Ling Ho, Ming Hung Tsai, Yu Hsin Hsieh, Teh Ia Huo, Ching Chih Chang, Fa Yauh Lee*, Hui Chun Huang, Ming Chih Hou, Shou Dong Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Introduction and Objectives: Liver cirrhosis is characterized by increased intrahepatic resistance, splanchnic vasodilation/angiogenesis, and formation of portosystemic collateral vessels. Collaterals can cause lethal complications such as gastroesophageal variceal hemorrhage. Homocysteine is linked to vascular dysfunction and angiogenesis and higher levels have been reported in cirrhotic patients. It is also known that folic acid supplementation reverses the effects of homocysteine. However, the treatment effect in cirrhosis has yet to be investigated. Material and methods: Liver cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (CBDL). The CBDL rats randomly received (1) vehicle; (2) DL-homocysteine thiolactone (1 g/kg/day); (3) DL-homocysteine thiolactone plus folic acid (100 mg/kg/day); or (4) folic acid. On the 29th day, hemodynamic parameters, liver and renal biochemistry, protein expressions of proangiogenic factors, mesenteric vascular density and portosystemic shunting were evaluated. Results: In the cirrhotic rats, homocysteine increased mesenteric vascular density and the severity of shunting. It also up-regulated the protein expressions of mesenteric vascular endothelial growth factor (VEGF) and phosphorylated-endothelial nitric oxide synthase (p-eNOS). These effects were reversed by folic acid treatment (P < 0.05). Conclusion: Folic acid ameliorated the adverse effects of homocysteine in the cirrhotic rats, which may be related to down-regulation of the VEGF-NO signaling pathway.

Original languageEnglish
Pages (from-to)633-639
Number of pages7
JournalAnnals of Hepatology
Issue number4
StatePublished - 1 Jul 2019


  • Angiogenesis
  • Folic acid
  • Homocysteine
  • Liver cirrhosis
  • Portosystemic collaterals


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