Clinical Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 28, 2006; 12(4): 588-594
Published online Jan 28, 2006. doi: 10.3748/wjg.v12.i4.588
Nitric oxide synthase and heme oxygenase expressions in human liver cirrhosis
Beatrice J Goh, Bee Tee Tan, Wei Min Hon, Kang Hoe Lee, Hoon Eng Khoo
Beatrice J Goh, Hoon Eng Khoo, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore
Bee Tee Tan, Kang Hoe Lee, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore
Wei Min Hon, Research Biolabs Pte Ltd, Yong Loo Lin School of Medicine, National University of Singapore
Supported by Research Biolabs Pte Ltd. Beatrice J Goh is a recipient of the Research Scholarship awarded by the National University of Singapore
Correspondence to: Dr. Khoo Hoon Eng, Department of Biochemistry, Faculty of Medicine, National University of Singapore, Block MD4A, #01-03 5 Science Drive 2, 117597, Singapore. bchkhe@nus.edu.sg
Telephone: +65-68743250 Fax: +65-67791453
Received: March 17, 2005
Revised: June 28, 2005
Accepted: August 3, 2005
Published online: January 28, 2006
Abstract

AIM: Portal hypertension is a common complication of liver cirrhosis. Intrahepatic pressure can be elevated in several ways. Abnormal architecture affecting the vasculature, an increase in vasoconstrictors and increased circulation from the splanchnic viscera into the portal system may all contribute. It follows that endogenous vasodilators may be able to alleviate the hypertension. We therefore aimed to investigate the levels of endogenous vasodilators, nitric oxide (NO) and carbon monoxide (CO) through the expression of nitric oxide synthase (NOS) and heme oxygenase (HO).

METHOD: Cirrhotic (n = 20) and non-cirrhotic (n = 20) livers were obtained from patients who had undergone surgery. The mRNA and protein expressions of the various isoforms of NOS and HO were examined using competitive PCR, Western Blot and immunohistochemistry.

RESULTS: There was no significant change in either inducible NOS (iNOS) or neuronal NOS (nNOS) expressions while endothelial NOS (eNOS) was up-regulated in cirrhotic livers. Concomitantly, caveolin-1, an established down-regulator of eNOS, was up-regulated. Inducible HO-1 and constitutive HO-2 were found to show increased expression in cirrhotic livers albeit in different localizations.

CONCLUSION: The differences of NOS expression might be due to their differing roles in maintaining liver homeostasis and/or involvement in the pathology of cirrhosis. Sheer stress within the hypertensive liver may induce increased expression of eNOS. In turn, caveolin-1 is also increased. Whether this serves as a defense mechanism against further cirrhosis or is a consequence of cirrhosis, is yet unknown. The elevated expression of HO-1 and HO-2 suggest that CO may compensate in its role as a vasodilator albeit weakly. It is possible that CO and NO have parallel or coordinated functions within the liver and may work antagonistically in the pathophysiology of portal hypertension.

Keywords: Liver cirrhosis, Nitric oxide synthase, Heme oxygenase, Gene expression, Competitive PCR