Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 7, 2006; 12(13): 2016-2023
Published online Apr 7, 2006. doi: 10.3748/wjg.v12.i13.2016
Adeno-associated virus-mediated heme oxygenase-1 gene transfer suppresses the progression of micronodular cirrhosis in rats
Tung-Yu Tsui, Chi-Keung Lau, Jian Ma, Gabriel Glockzin, Aiman Obed, Hans J Schlitt, Sheung-Tat Fan
Tung-Yu Tsui, Chi-Keung Lau, Jian Ma, Sheung-Tat Fan, Centre for the Study of Liver Disease and Department of Surgery, the University of Hong Kong, Pokfulam, Hong Kong
Tung-Yu Tsui, Gabriel Glockzin, Aiman Obed, Hans J Schlitt, Department of Surgery, University of Regensburg Medical Centre, Regensburg, Germany
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Tung-Yu Tsui, Department of Surgery, University of Regensburg Medical Centre, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. tung-yu.tsui@klinik.uni-regensburg.de
Telephone: +49-941-9446852 Fax: +49-941-9446802
Received: September 12, 2005
Revised: October 15, 2005
Accepted: October 26, 2005
Published online: April 7, 2006
Abstract

AIM: To test the hypothesis that enhancement of the activity of heme oxygenase can interfere with processes of fibrogenesis associated with recurrent liver injury, we investigated the therapeutic potential of over-expression of heme oxygense-1 in a CCl4-induced micronodular cirrhosis model.

METHODS: Recombinant adeno-associated viruses carrying rat HO-1 or GFP gene were generated. 1×1012 vg of adeno-associated viruses were administered through portal injection at the time of the induction of liver fibrosis.

RESULTS: Conditioning the rat liver with over-expression of HO-1 by rAAV/HO-1 significantly increased the HO enzymatic activities in a stable manner. The development of micronodular cirrhosis was significantly inhibited in rAAV/HO-1-transduced animals as compared to controls. Portal hypertension was markedly diminished in rAAV/HO-1-transduced animals as compared to controls, whereas there are no significant changes in systolic blood pressure. This finding was accompanied with improved liver biochemistry, less infiltrating macrophages and less activated hepatic stellate cells (HSCs) in rAAV/HO-1-transduced livers.

CONCLUSIONS: Enhancement of HO activity in the livers suppresses the development of cirrhosis.

Keywords: Cirrhosis, Portal hypertension, Heme oxygenase, Gene therapy, Adeno-associated virus