The significance of chymase in the progression of abdominal aortic aneurysms in dogs.

Abstract

In this study, we investigated the effect of a specific chymase inhibitor, NK3201, in the progression of abdominal aortic aneurysm in a dog experimental model. Abdominal aortic aneurysms were induced in dogs by injecting elastase into the abdominal aorta. NK3201 (1 mg/kg per day, p.o.) or a placebo was started 3 days before elastase injection and continued for 8 weeks after the injection. On abdominal ultrasound, the aortic diameter was seen to gradually expand in the placebo-treated group, but not in the NK3201-treated group. Eight weeks after elastase injection, the ratio of the medial area to the total area in the placebo-treated group was significantly smaller than that in the normal group, but it was significantly larger than that in the NK3201-treated group. In addition to chymase activity, angiotensin II-forming and matrix metalloproteinase-9 activities were significantly higher in the placebo-treated group than in the normal group; in the NK3201-treated group, all of these activities were significantly decreased. On immunohistochemical analyses, there was a significantly greater number of chymase-positive cells in the placebo-treated group than in the normal group, but the number was significantly smaller in the NK3201-treated group than in the placebo-treated group. Thus, chymase inhibition may become a useful strategy for preventing abdominal aortic aneurysms.

• Authors: Keiichi Furubayashi, Shinji Takai, Denan Jin, Michiko Muramatsu, Toshihiko Ibaraki, Masayoshi Nishimoto, Hitoshi Fukumoto, Takahiro Katsumata, Mizuo Miyazaki
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 30 Issue 4 Pg. 349-57 (Apr 2007) ISSN: 0916-9636 [Print] England
• PMID: 17541214 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetamides
• Matrix Metalloproteinase Inhibitors
• NK3201
• Pyrimidines
• Angiotensin II
• Chymases
• Matrix Metalloproteinase 9

Topics

• Acetamides (pharmacology)
• Angiotensin II (physiology)
• Animals
• Aorta, Abdominal (diagnostic imaging, drug effects, enzymology)
• Aortic Aneurysm, Abdominal (etiology, physiopathology, prevention & control)
• Cell Count
• Chymases (antagonists & inhibitors, physiology)
• Disease Models, Animal
• Disease Progression
• Dogs
• Male
• Matrix Metalloproteinase 9 (physiology)
• Matrix Metalloproteinase Inhibitors
• Neutrophils (drug effects, pathology)
• Pyrimidines (pharmacology)
• Tunica Media (drug effects, pathology)
• Ultrasonography