Altered expression of heme oxygenase-1 in the livers of patients with portal hypertensive diseases

N. Makino, M. Suematsu, Y. Sugiura, H. Morikawa, S. Shiomi, N. Goda, T. Sano, Y. Nimura, K. Sugimachi, Y. Ishimura

Research output: Contribution to journalArticle

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Abstract

This study was designed to determine changes in expression of heme oxygenase (HO)-1, the stress-inducible and carbon monoxide-producing enzyme, in normotensive and portal hypertensive human livers. GTS-1, a monoclonal antibody against rat HO-1 cross-reacted with the human HO-1 and blocked its enzyme activity, allowing us to examine the activity and localization of HO-1. In controls, approximately 50% of the total HO activity was from HO-1 as judged by the sensitivity to GTS-1, while the rest of activity was from other isozymes such as HO-2, HO-1 was expressed mainly in a subpopulation of Kupffer cells, and the expression in hepatic stellate cells, sinusoidal endothelial cells, and hepatocytes was little, if any. The HO-1 expression exhibited quite different pictures in the livers of portal hypertensive diseases. In cirrhotic livers, which undergo portal hypertension through increases in intrasinusoidal resistance and regenerative changes in the parenchyma, HO-1 occurred in a majority of Kupffer cells and was also observed in hepatocytes. Consequently, the total HO-1 activities became significantly greater in these tissues than those from normal individuals. By contrast, livers of idiopathic portal hypertension that are characterized by an increase in presinusoidal resistance displayed a significant decrease in the HO-1 expression in Kupffer cells, and its hepatocellular expression was not detectable. Although factors involved in altered HO-1 expression in these cells remain unknown, the results suggest that Kupffer cells could alter their expression of HO-1 in response to local hemodynamic changes associated with chronic portal hypertension in humans.

Original languageEnglish
Pages (from-to)32-42
Number of pages11
JournalHepatology
Volume33
Issue number1
DOIs
Publication statusPublished - 2001

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Heme Oxygenase-1
Liver
Kupffer Cells
Portal Hypertension
Hepatocytes
Heme Oxygenase (Decyclizing)
Hepatic Stellate Cells
Enzymes
Carbon Monoxide
Isoenzymes
Endothelial Cells
Hemodynamics
Monoclonal Antibodies

ASJC Scopus subject areas

  • Hepatology

Cite this

Makino, N., Suematsu, M., Sugiura, Y., Morikawa, H., Shiomi, S., Goda, N., ... Ishimura, Y. (2001). Altered expression of heme oxygenase-1 in the livers of patients with portal hypertensive diseases. Hepatology, 33(1), 32-42. https://doi.org/10.1053/jhep.2001.21161

Altered expression of heme oxygenase-1 in the livers of patients with portal hypertensive diseases. / Makino, N.; Suematsu, M.; Sugiura, Y.; Morikawa, H.; Shiomi, S.; Goda, N.; Sano, T.; Nimura, Y.; Sugimachi, K.; Ishimura, Y.

In: Hepatology, Vol. 33, No. 1, 2001, p. 32-42.

Research output: Contribution to journalArticle

Makino, N, Suematsu, M, Sugiura, Y, Morikawa, H, Shiomi, S, Goda, N, Sano, T, Nimura, Y, Sugimachi, K & Ishimura, Y 2001, 'Altered expression of heme oxygenase-1 in the livers of patients with portal hypertensive diseases', Hepatology, vol. 33, no. 1, pp. 32-42. https://doi.org/10.1053/jhep.2001.21161
Makino, N. ; Suematsu, M. ; Sugiura, Y. ; Morikawa, H. ; Shiomi, S. ; Goda, N. ; Sano, T. ; Nimura, Y. ; Sugimachi, K. ; Ishimura, Y. / Altered expression of heme oxygenase-1 in the livers of patients with portal hypertensive diseases. In: Hepatology. 2001 ; Vol. 33, No. 1. pp. 32-42.
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