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Significance of chymase‐dependent angiotensin II formation in the progression of human liver fibrosis
Author(s) -
Komeda Koji,
Jin Denan,
Takai Shinji,
Hayashi Michihiro,
Takeshita Atsushi,
Shibayama Yuro,
Tanigawa Nobuhiko,
Miyazaki Mizuo
Publication year - 2008
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2007.00271.x
Subject(s) - chymase , cirrhosis , angiotensin ii , angiotensin converting enzyme , medicine , fibrosis , renin–angiotensin system , hepatic stellate cell , endocrinology , gastroenterology , immunology , mast cell , receptor , blood pressure
Aim: Angiotensin II may contribute to liver fibrogenesis. In addition to angiotensin‐converting enzyme (ACE), chymase, which is expressed by mast cells, is also known to be an angiotensin II‐forming enzyme. However, it is unclear which of these two angiotensin II‐forming enzymes plays a more important role in liver cirrhosis progression. In the present study, the role of angiotensin II‐forming enzymes in the progression of liver cirrhosis was clarified. Methods: A total of 77 patients (16 in F0 stage, 10 in F1 stage, 22 in F2 stage, 12 in F3 stage, and 17 in F4 stage) were classified according to the new Inuyama classification into a non‐cirrhosis (F0) group, an early cirrhosis (F1 + F2) group, and a chronic cirrhosis (F3 + F4) group. Results: Both chymase and total angiotensin II‐forming activities were significantly higher in chronic cirrhosis patients than in the other two groups. However, there was nodifference among the three groups in ACE activity. On immunohistology, the number of chymase‐ and angiotensin II‐positive cells was significantly higher in the chronic cirrhosis group than in the non‐cirrhosis and early cirrhosis groups. There were significant correlations between the number of chymase‐positive cells and the number of angiotensin II‐positive cells, between the number of chymase‐positive cells and the degree of fibrosis, and between the number of angiotensin II‐positive cells and the degree of fibrosis. Conclusion: These results suggest that chymase‐dependent angiotensin II formation may play an important role in hepatic fibrosis of patients with cirrhosis.