Tryptase promotes atherosclerotic plaque haemorrhage in ApoE-/- mice.
Tryptase promotes atherosclerotic plaque haemorrhage in ApoE-/- mice.
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类胰蛋白酶促进 ApoE-/- 小鼠动脉粥样硬化斑块出血
DOI：
10.1371/journal.pone.0060960
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yin L
中科院分区：
文献类型：
--
作者：
Zhi X;Xu C;Zhang H;Tian D;Li X;Ning Y;Yin L
类胰蛋白酶是肥大细胞(MC)颗粒蛋白中含量最丰富的一种，在动脉粥样硬化斑块的形成中起着重要作用。为了验证类胰蛋白酶直接参与动脉粥样硬化斑块出血的假设，将类胰蛋白酶基因序列和siRNA克隆到慢病毒载体中，建立了ApoE-/-小鼠动脉粥样硬化斑块出血模型。颈动脉袖套手术后，将小鼠随机分为6组。苏木精-伊红(HE)染色显示类胰蛋白酶高表达组颈动脉斑块面积明显大于其他组，动脉狭窄程度更大。除siRNA组外，其余各组袖套侧动脉狭窄率均大于90%。类胰蛋白酶显著促进斑块出血，因为在类胰蛋白酶过度表达组的小鼠中有50%的小鼠有斑块出血，而在siRNA组中只有10%。颈动脉斑块免疫组织化学染色显示，类胰蛋白酶高表达组纤溶酶原激活物抑制物-1(PAI-1)表达最低，组织纤溶酶原激活物(TPA)、CD31、CD34和血管内皮生长因子(VEGF)表达最高。这一观察结果与siRNA组的观察结果完全相反。类胰蛋白酶促进bEnd.3细胞的生长、迁移和毛细血管样管的形成，提示类胰蛋白酶具有促进微血管生成的作用。在bEnd.3细胞中，类胰蛋白酶抑制PAI-1的表达，上调tPA的表达。我们在体内和体外的研究表明，胰酶可能通过促进血管生成和调节PAI-1/tPA的平衡来促进动脉粥样硬化斑块出血。因此，调节MCs中类胰蛋白酶的表达可能为动脉粥样硬化的治疗提供一个潜在的靶点。
Tryptase, the most abundant mast cell (MC) granule protein, plays an important role in atherosclerosis plaque development. To test the hypothesis that tryptase participates directly in atherosclerosis plaque haemorrhage, the gene sequence and siRNA for tryptase were cloned into a lentivirus carrier and atherosclerosis plaque haemorrhage models in ApoE-/- mice were constructed. After a cuffing-cervical artery operation, the mice were randomly divided into 6 groups. Hematoxylin and eosin(HE) staining showed that the cervical artery plaque area was much larger in the tryptase overexpression group compared to the other groups, and there was greater artery stenosis. The artery stenosis from the cuff-side in all groups was more than 90%, except the siRNA group. Tryptase promotes plaque haemorrhage distinctively because 50% of the mice in the tryptase overexpression group had plaque haemorrhage, while only 10% in the siRNA group did. The immunohistochemistry of the cervical artery plaque showed that plasminogen activator inhibitor-1 (PAI-1) expression was the lowest while tissue plasminogen activator (tPA), CD31, CD34 and VEGF was the highest in the tryptase overexpression groups. This observation was completely contrary to what was observed in the siRNA group. Tryptase promoted bEnd.3 cell growth, migration and capillary-like tube formation, which suggests that tryptase can promote microvessel angiogenesis. PAI-1 expression was inhibited, while tPA expression was increased by tryptase in bEnd.3 cells. Our in vivo and in vitro studies suggest that trypase can promote atherosclerotic plaque haemorrhage by promoting angiogenesis and regulating the balance of PAI-1 and tPA. Thus, regulating tryptase expression in MCs may provide a potential target for atherosclerosis treatment.
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DOI：
10.1161/01.atv.18.11.1707
发表时间：
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影响因子：
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