Effects of chymase inhibitor on angiotensin II-induced abdominal aortic aneurysm development in apolipoprotein E-deficient mice
Effects of chymase inhibitor on angiotensin II-induced abdominal aortic aneurysm development in apolipoprotein E-deficient mice
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DOI：
10.1016/j.atherosclerosis.2008.09.032
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发表时间：
2009-06-01
期刊：
影响因子：
5.3
通讯作者：
Miyazaki, Mizuo
中科院分区：
文献类型：
--
作者：
Inoue, Nao;Muramatsu, Michiko;Miyazaki, Mizuo
目的：切酶可能通过基质金属蛋白酶(MMP)-9的活化在腹主动脉瘤（AAA）的发生发展中起重要作用。本研究的目的是确定chymase是否参与血管紧张素（Ang） ii诱导的载脂蛋白E （apoE）缺陷小鼠AAA的发生。方法与结果：本研究以16周龄apoe缺陷雄性小鼠为研究对象，分别给予Ang II （1000ng/kg/min；载药组）或生理盐水（生理盐水组）4周。为了研究乳糜酶抑制对AAA发展的影响，在注射Ang 11的同时口服NK3201 （30 mg/kg/天）。在Ang ii治疗的载药组中，腹主动脉的肾上区出现了AAAs，但在生理盐水组中未观察到AAAs。另一方面，NK3201显著抑制了Ang ii处理的小鼠组AAAs的严重程度和管腔面积。Ang ii + nk3201处理组的MMP-9活性明显低于Ang ii处理的载体组。此外，Ang ii + nk3201处理组单核/巨噬细胞明显少于Ang ii处理的对照组。结论：Chymase参与了angii诱导的apoe缺陷小鼠AAA的发生。2008爱思唯尔爱尔兰有限公司版权所有。
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.