Hepatocyte expression of angiotensin II type 1 receptor is downregulated in advanced human liver fibrosis.

BACKGROUND: The renin-angiotensin system plays an important role in fibrosis. Angiotensin II regulates key steps in tissue remodelling processes through angiotensin II type 1 receptor (AT1R). In bile duct-occluded rats, AT1R expression is significantly decreased in advanced liver fibrosis. Therefore, we studied the AT1R expression in human liver tissue during different stages of fibrosis caused by chronic hepatitis C. METHODS: Liver biopsy specimens from 85 patients were analysed. Real-time reverse transcription polymerase chain reaction was used to quantify AT1R mRNA. Immunohistochemical labelling of AT1R and double staining for AT1R, CD31, CD68, CD3 and fibulin-2 were performed. RESULTS: AT1R mRNA was significantly reduced in human liver tissue with end-stage cirrhosis compared with early fibrosis. In liver cirrhosis, immunohistochemistry revealed a decreased expression of AT1R on hepatocytes, together with an increased staining intensity on myofibroblasts, vascular endothelium and bile duct epithelium. CONCLUSION: In conclusion, AT1R expression is downregulated in human liver cirrhosis specimens because of the reduced expression levels on hepatocytes. Therefore, antifibrogenic therapy with AT1R blockers may be most promising if initiated during early stages of fibrosis.