Effect of CVX-060 treatment on hepatic gene expression of cirrhotic rats

Currently, the therapeutic prospects for cirrhosis patients are limited to liver transplantation and, therefore, there is an urgent need to develop new therapeutic strategies for improved treatments. Cirrhosis was induced in male Wistar rats with CCl4 treatment, and RNA from the complete livers was extracted and quantified through microarray experiments. Angiopoietins signalling is a key pathway in blood vessel normalization. Angiopoietin 1 (Ang1)-Tie2 signalling stabilizes blood vessels, Angiopoietin 2 (Ang2) on the other hand is a context-dependent antagonist of Ang1 and decreases its stabilizing effect giving rise to immature blood vessels. Cirrhotic conditions are characterized by higher expression and activity of Ang2 than healthy conditions, resulting in the loss of blood vessels stability. Previous work showed that inhibition of Ang2 via CVX-060 enhances Ang1-Tie2 signalling, and can stabilize the vascular system in cirrhotic livers. We therefore performed RNA extraction after treatment of cirrhotic rats with CVX-060 during 4 weeks. We observed changes in expression state (expressed/not expressed) in key transcription factors previously implicated in cirrhosis. To induce cirrhosis, male Wistar rats were exposed to inhalation of CCl4, as previously described. Five cirrhotic rats were treated once a week with 10 mg/kg of CVX-060 (Pfizer, Inc., New York, NY, USA) for 4 weeks. CVX-060 was diluted in 500 l of saline solution and injected intravenously via the tail vein. In parallel, another group of cirrhotic rats (n=5) was injected with vehicle, as a treatment control. Gene expression in CCl4 and CCl4+CVX-060 treated livers was quantified using Affymetrix GeneChip Rat Genome 230.2 Array. The protocols comply with the criteria of the investigation and ethics committee of the Hospital Clínic Universitari and the University of Barcelona.