JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on January 21, 2003; DOI: 10.1124/jpet.102.045179

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.102.045179v1
305/1/17    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Takai, S.
Right arrow Articles by Miyazaki, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takai, S.
Right arrow Articles by Miyazaki, M.

Vol. 305, Issue 1, 17-23, April 2003

A Novel Chymase Inhibitor, 4-[1-{[bis-(4-Methyl-phenyl)-methyl]-carbamoyl}-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid (BCEAB), Suppressed Cardiac Fibrosis in Cardiomyopathic Hamsters

Shinji Takai, Denan Jin, Masato Sakaguchi , Satoru Katayama , Michiko Muramatsu , Minoru Sakaguchi, Eiko Matsumura, Shokei Kim and Mizuo Miyazaki

Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka, Japan (S.T., D.J., M.S., M.M., M.M.); Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, Takatsuki City, Osaka, Japan (S.K., M.S., E.M.); and Department of Pharmacology, Osaka City University Medical School, Abeno-ku, Osaka, Japan (S.K.)

Previously, we reported that levels of chymase activity and its mRNA in cardiac tissues were significantly increased along with progression of cardiac fibrosis in cardiomyopathic hamsters, but the involvement of chymase in the progression of fibrosis has been unclear. In cultured human fibroblasts, the concentration of transforming growth factor-beta in the supernatant of medium was significantly increased after injection of human chymase. Furthermore, human chymase dose dependently increased cell proliferation, and this chymase-dependent proliferation was completely suppressed by a chymase inhibitor, Suc-Val-Pro-Phep(OPh)2 (10 µM) or an anti-transforming growth factor-beta antibody (100 µg/ml). In this study, we used Bio14.6 and F1B hamsters as cardiomyopathic and control hamsters, respectively. Cardiomyopathic hamsters were orally administered a novel chymase inhibitor, 4-[1-{[bis-(4-methylphenyl)-methyl]-carbamoyl}-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid (BCEAB; 100 mg/kg per day), or placebo from 5- to 45-week-old. In the placebo-treated group, the cardiac chymase activity in cardiomyopathic hamsters 45 weeks old was significantly increased compared with that in control hamsters. BCEAB significantly reduced the cardiac chymase activity. The indexes (+dP/dt and -dP/dt) of cardiac function were significantly improved by treatment with BCEAB. The mRNA levels of collagen I and collagen III in the placebo-treated hamsters were significantly reduced to 69.6 and 76.5% by treatment with BCEAB, respectively. The fibrotic area in cardiac tissues in the BCEAB-treated hamsters was significantly suppressed to 50.7% compared with that in the placebo-treated treated hamsters. Therefore, the activation of transforming growth factor-beta by chymase may play an important role in the progression of cardiac fibrosis and cardiac dysfunction in cardiomyopathy.

0022-3565/03/3051-0017$07.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2003 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Eur. J. Cardiothorac. Surg.Home page
H. Kanemitsu, S. Takai, H. Tsuneyoshi, E. Yoshikawa, T. Nishina, M. Miyazaki, T. Ikeda, and M. Komeda
Chronic chymase inhibition preserves cardiac function after left ventricular repair in rats
Eur. J. Cardiothorac. Surg., January 1, 2008; 33(1): 25 - 31.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
S. S. Palaniyandi, Y. Nagai, K. Watanabe, M. Ma, P. T. Veeraveedu, P. Prakash, F. A. Kamal, Y. Abe, K. Yamaguchi, H. Tachikawa, et al.
Chymase Inhibition Reduces the Progression to Heart Failure After Autoimmune Myocarditis in Rats
Experimental Biology and Medicine, October 1, 2007; 232(9): 1213 - 1221.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
S R Atkins, E L Matteson, J L Myers, J H Ryu, and T Bongartz
Morphological and quantitative assessment of mast cells in rheumatoid arthritis associated non-specific interstitial pneumonia and usual interstitial pneumonia.
Ann Rheum Dis, May 1, 2006; 65(5): 677 - 680.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
S. Takai, T. Ibaraki, M. Muramatsu, and M. Miyazaki
Reply to akgul and noon.
Eur. J. Cardiothorac. Surg., April 1, 2006; 29(4): 638 - 638.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. Jin, H. Ueda, S. Takai, Y. Okamoto, M. Muramatsu, M. Sakaguchi, N. Shibahara, Y. Katsuoka, and M. Miyazaki
Effect of Chymase Inhibition on the Arteriovenous Fistula Stenosis in Dogs
J. Am. Soc. Nephrol., April 1, 2005; 16(4): 1024 - 1034.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Tchougounova, A. Lundequist, I. Fajardo, J.-O. Winberg, M. Abrink, and G. Pejler
A Key Role for Mast Cell Chymase in the Activation of Pro-matrix Metalloprotease-9 and Pro-matrix Metalloprotease-2
J. Biol. Chem., March 11, 2005; 280(10): 9291 - 9296.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K. Tsunemi, S. Takai, M. Nishimoto, D. Jin, M. Sakaguchi, M. Muramatsu, A. Yuda, S. Sasaki, and M. Miyazaki
A Specific Chymase Inhibitor, 2-(5-Formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[{3,4-dioxo-1-phenyl-7-(2-pyridyloxy)}-2-heptyl]acetamide (NK3201), Suppresses Development of Abdominal Aortic Aneurysm in Hamsters
J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 879 - 883.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. Jin, S. Takai, M. Sakaguchi, Y. Okamoto, M. Muramatsu, and M. Miyazaki
An Antiarrhythmic Effect of a Chymase Inhibitor after Myocardial Infarction
J. Pharmacol. Exp. Ther., May 1, 2004; 309(2): 490 - 497.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
E. Ritz
Chymase: A Potential Culprit in Diabetic Nephropathy?
J. Am. Soc. Nephrol., July 1, 2003; 14(7): 1952 - 1954.
[Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2003 by the American Society for Pharmacology and Experimental Therapeutics.