NDLI: Suppression of basic fibroblast growth factor-induced angiogenesis by a specific chymase inhibitor, BCEAB, through the chymase-angiotensin-dependent pathway in hamster sponge granulomas

Content Provider	PubMed Central
Author	Muramatsu, Michiko Yamada, Mayumi Takai, Shinji Miyazaki, Mizuo
Copyright Year	2002
Abstract	We investigated the profound involvement of mast cell chymase, an alternative angiotensin II-generating enzyme, in angiogenesis using a specific chymase inhibitor. We also studied the functional profiles of this novel inhibitor in basic fibroblast growth factor (bFGF)-induced angiogenesis. In this study, angiogenesis was induced by daily injections of bFGF (0.3 μg site−1 day−1), angiotensin I (2 nmol site−1 day−1) or angiotensin II (2 nmol site−1 day−1) into sponges implanted to male hamsters subcutaneously for 7 days. Angiogenesis in the granulation tissue surrounding sponges was evaluated by measuring the haemoglobin (Hb) content and local blood flow as the parameters for angiogenesis. A chymase inhibitor, BCEAB (4-[1-{[bis-(4-methyl-phenyl)-methyl]-carbamoyl}-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid), was simultaneously administered into the implanted sponges (2 or 5 nmol site−1 day−1, for 7 days) treated with bFGF and strongly suppressed the haemoglobin contents in sponge granulomas. In the studies using a laser doppler perfusion imager, BCEAB (5 nmol site−1 day−1) also attenuated the bFGF-induced increase of local blood flow around the implanted sponge granuloma. In bFGF-induced angiogenesis, chymase activity in sponge granulomas was substantially increased. It was also confirmed that the chymase activity increased by bFGF was significantly and dose-dependently inhibited by BCEAB (2, 5 nmol site−1 day−1). BCEAB inhibited the Hb contents and the expression of vascular endothelial growth factor (VEGF) mRNA induced by angiotensin I but not by angiotensin II. These results suggest that the significance of chymase in bFGF-induced angiogenesis was confirmed, and a novel inhibitor, BCEAB, strongly suppresses the bFGF-induced angiogenesis through the chymase-angiotensin II-VEGF dependent pathway.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0704893
Ending Page	560
Page Count	7
Starting Page	554
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	4
Volume Number	137
Language	English
Publisher Date	2002-10-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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