Effects of chymase inhibitor on angiotensin II-induced abdominal aortic aneurysm development in apolipoprotein E-deficient mice.
OBJECTIVE
Chymase may play an important role in abdominal aortic aneurysm (AAA) development through matrix metalloproteinase (MMP)-9 activation. The purpose of this study was to determine whether chymase is involved in angiotensin (Ang) II-induced AAA development in apolipoprotein E (apoE)-deficient mice.


RESULTS
In this study, Ang II (1000 ng/kg/min; vehicle group) or saline (saline group) was administered to 16-week-old, male, apoE-deficient mice for 4 weeks. To examine the effects of chymase inhibition on AAA development, oral NK3201 (30 mg/kg/day) was given for the same period as the Ang II infusion. AAAs developed at the suprarenal region of the abdominal aorta in the Ang II-treated vehicle group, but they were not observed in the saline group. On the other hand, the severity and luminal area of the AAAs in the Ang II-treated vehicle group were significantly suppressed by NK3201 treatment. MMP-9 activity was significantly lower in the Ang II-treated+NK3201-treated group than in the Ang II-treated vehicle group. Furthermore, there were significantly fewer monocyte/macrophage cells in the Ang II-treated+NK3201-treated group than in the Ang II-treated vehicle group.


CONCLUSIONS
Chymase is involved in Ang II-induced AAA development in apoE-deficient mice.
Inoue
Nao
N
Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan.
Muramatsu
Michiko
M
Jin
Denan
D
Takai
Shinji
S
Hayashi
Tetsuya
T
Katayama
Hiroshi
H
Kitaura
Yasushi
Y
Tamai
Hiroshi
H
Miyazaki
Mizuo
M
D000081:Acetamides / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000804:Angiotensin II; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D053818:Chymases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D000081:Acetamides; D001057:Apolipoproteins E; D004792:Enzyme Precursors; C437945:NK3201; D011743:Pyrimidines; D015842:Serine Proteinase Inhibitors; D000804:Angiotensin II; D002784:Cholesterol; D053818:Chymases; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse