Effects of long term ethanol consumption mediated oxidative stress on neovessel generation in liver

Toxicol Mech Methods. 2012 Jun;22(5):375-82. doi: 10.3109/15376516.2012.666651. Epub 2012 Mar 17.


Angiogenesis, the growth of new blood vessels, is essential during tissue repair. Though most molecular mechanisms of angiogenesis are common to the liver and other organs, there was no report available whether alcoholic liver disease also causes angiogenesis. In this study, we examined the effects of long term ethanol (1.6 g/kg body weight/day) consumption on angiogenic responses in the liver of male Wistar strain albino rats (16-18 weeks old, weighing 200-220 g) up to 36 weeks. Chronic ethanol consumption was associated with not only elevated oxidative stress, and altered cytokines expression, but also developed large von Willebrand factor, fibrosis and activation of matrix metalloproteinases. Moreover, vascular endothelial growth factor-receptor 2 (VEGF-R2, fetal liver kinase 1: Flk-1/KDR) expression and neovessel generation in the rat liver were noted after 36 weeks of ethanol consumption. Thus our study provides novel evidence that long-term ethanol consumption is associated with angiogenesis through delicate and coordinated action of a variety of mediators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia / drug effects
  • Cytokines / biosynthesis
  • Ethanol / administration & dosage
  • Ethanol / toxicity*
  • Fibrosis
  • Liver / blood supply*
  • Liver / drug effects
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases, Alcoholic / immunology
  • Liver Diseases, Alcoholic / metabolism*
  • Liver Diseases, Alcoholic / pathology
  • Liver Function Tests
  • Male
  • Matrix Metalloproteinases / metabolism
  • Neovascularization, Pathologic / chemically induced*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Time Factors
  • Vascular Endothelial Growth Factor Receptor-2 / biosynthesis
  • von Willebrand Factor / biosynthesis


  • Cytokines
  • von Willebrand Factor
  • Ethanol
  • Vascular Endothelial Growth Factor Receptor-2
  • Matrix Metalloproteinases