Intestinal and plasma VEGF levels in cirrhosis: the role of portal pressure

J Cell Mol Med. 2012 May;16(5):1125-33. doi: 10.1111/j.1582-4934.2011.01399.x.

Abstract

Increased levels of intestinal VEGF are thought to worsen portal hypertension. The cause of the increase in the level of intestinal VEGF found during cirrhosis is not known. The aim of this study is to demonstrate a relationship between portal pressure (PP) and intestinal/ plasma VEGF levels in different stages of fibrosis/cirrhosis. In this experiment, rats were exposed to carbon tetrachloride (CCl(4) ) for 6, 8 and 12 weeks. At the end of exposure, the three groups of rats exhibited three different stages of pathology: non-cirrhotic, early fibrotic and cirrhotic, respectively. For those rats and their age-matched controls, PP and intestinal/plasma VEGF levels were measured. Rats inhaling CCl(4) for 12 weeks developed portal hypertension (18.02 ± 1.07 mmHg), while those exposed for 6 weeks (7.26 ± 0.58 mmHg) and for 8 weeks (8.55 ± 0.53 mmHg) did not. The rats exposed for 12 weeks also showed a 40% increase in the level of intestinal VEGF compared to the controls (P < 0.05), while those rats exposed to CCl(4) inhalation for 6 and 8 weeks did not. There was a significant positive correlation between PP and intestinal VEGF levels (r(2) = 0.4, P < 0.005). Plasma VEGF levels were significantly elevated in those rats exposed to 12 weeks of CCl(4) inhalation (63.7 pg/ml, P < 0.01), compared to the controls (8.5 pg/ml). However, no correlation was observed between PP and plasma VEGF levels. It is concluded that portal pressure modulates intestinal VEGF levels during the development of cirrhosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carbon Tetrachloride Poisoning / complications
  • Hypertension, Portal / chemically induced
  • Hypertension, Portal / metabolism*
  • Intestines / chemistry*
  • Liver / chemistry
  • Liver / pathology
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / metabolism*
  • Liver Cirrhosis, Experimental / pathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / blood*

Substances

  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat