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. Methods and results: In this study, Ang II (1000ng/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 11 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.