The significance of chymase in the progression of abdominal aortic aneurysms in dogs.
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.
Furubayashi
Keiichi
K
Department of Pharmacology, Osaka Medical College, Takatsuki, Japan.
Takai
Shinji
S
Jin
Denan
D
Muramatsu
Michiko
M
Ibaraki
Toshihiko
T
Nishimoto
Masayoshi
M
Fukumoto
Hitoshi
H
Katsumata
Takahiro
T
Miyazaki
Mizuo
M
D000081:Acetamides / Q000494:pharmacology*; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging / Q000187:drug effects / Q000201:enzymology*; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology* / Q000503:physiopathology* / Q000517:prevention & control; D002452:Cell Count; D053818:Chymases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D061965:Matrix Metalloproteinase Inhibitors; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011743:Pyrimidines / Q000494:pharmacology*; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology; D014463:Ultrasonography
D000081:Acetamides; D061965:Matrix Metalloproteinase Inhibitors; C437945:NK3201; D011743:Pyrimidines; D000804:Angiotensin II; D053818:Chymases; D020780:Matrix Metalloproteinase 9