中性粒细胞衍生的矩阵金属蛋白酶9触发了急性大动脉剖析
Tomohiro Kurihara1, Ryoko Shimizu-Hirota, Masayuki Shimoda
1Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan
Circulation
|November 9, 2012
概括
急性大动脉解剖 (AAD) 涉及中性粒细胞释放矩阵金属蛋白酶-9 (MMP9) 作为对血管新生II的反应. 抑制MMP9或消耗中性粒细胞可以显著降低AD发病率.
科学领域:
- 心血管生物学 心血管生物学
- 血管病理学 血管病理学
- 矩阵生物学 矩阵生物学
背景情况:
- 急性大动脉解剖 (AAD) 是一种严重的疾病,缺乏有效的药物治疗方法.
- 矩阵金属蛋白酶 (MMPs) 与血管疾病有关,但它们在AAD中的具体作用尚不清楚.
研究的目的:
- 调查MMPs在AAD病变发生中的作用.
- 确定关键的分子效应因子和驱动AAD的机制.
主要方法:
- 在AAD患者中选循环MMP.
- 开发了一种用于AAD的新型小鼠模型,使用血管新素II输注和lysyl氧化酶抑制剂.
- 在小鼠模型中服用MMP抑制剂和抗中性粒细胞抗体.
主要成果:
- 在AAD患者中增加MMP9和血管新生素II.
- 在具有高发病率的小鼠模型中成功诱导了AAD.
- 在切割的大动脉中观察到MMP9过度表达和中性粒细胞透.
- 抑制MMP和中性粒细胞枯竭显著降低了AAD发病率.
结论:
- 透到大动脉内脏的中性粒细胞释放MMP9作为对血管素II的反应,启动AAD.
- 在AAD发育中,MMP9起着至关重要的作用,独立于初始中性粒细胞透水平.
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