Indomethacin reduces rates of aortic dissection and rupture of the abdominal aorta by inhibiting monocyte/macrophage accumulation in a murine model
Indomethacin reduces rates of aortic dissection and rupture of the abdominal aorta by inhibiting monocyte/macrophage accumulation in a murine model
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DOI：
10.1038/s41598-019-46673-z
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发表时间：
2019-07-24
影响因子：
4.6
通讯作者：
Suzuki，Toru
中科院分区：
文献类型：
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作者：
Tomida，Shota;Aizawa，Kenichi;Suzuki，Toru
主动脉夹层是一种危及生命的疾病，其特征是主动脉壁的组成层分离。我们最近发现单核细胞/巨噬细胞浸润到主动脉壁是一种致病机制的条件。在本研究中，我们研究了消炎药吲哚美辛是否可以抑制主动脉壁中单核细胞/巨噬细胞的积聚和随后的夹层。向使用β-氨基丙腈（BAPN）和血管紧张素II（Ang II）输注诱导主动脉夹层的小鼠施用吲哚美辛（从每日口服施用前3天起）（2周）。吲哚美辛预防了腹主动脉夹层的死亡，并将主动脉夹层的发病率降低了40%。组织学和流式细胞术分析表明，吲哚美辛给药导致单核细胞跨内皮迁移和单核细胞/巨噬细胞在主动脉壁中积聚的抑制。这些结果表明，吲哚美辛给药降低了该病症的鼠模型中主动脉夹层的发病率。
Aortic dissection is a life-threatening condition, which is characterised by separation of the constituent layers of the aortic wall. We have recently shown that monocyte/macrophage infiltration into the aortic wall is a pathogenic mechanism of the condition. In the present study, we investigated whether the anti-inflammatory agent, indomethacin, could inhibit monocyte/macrophage accumulation in the aortic wall and ensuing dissection. Indomethacin was administered (from 3 days prior with daily oral administration) to mice in which aortic dissection was induced using beta-aminopropionitrile (BAPN) and angiotensin II (Ang II) infusion (2 weeks). Indomethacin prevented death from abdominal aortic dissection and decreased incidence of aortic dissection by as high as 40%. Histological and flow cytometry analyses showed that indomethacin administration resulted in inhibition of monocyte transendothelial migration and monocyte/macrophage accumulation in the aortic wall. These results indicate that indomethacin administration reduces rate of onset of aortic dissection in a murine model of the condition.