Circulation：蛋白酶激活受体-2参与血管炎症和动脉粥样硬化的发生

2018-10-24 MedSci MedSci原创

凝血系统与血管炎症密切相关，但其机制尚不明确。近期有研究表明蛋白酶激活受体（PAR）-2是激活因子X的主要受体，在血管细胞和白细胞中均有表达，提示PAR-2可能参与炎症病理过程。现研究人员对PAR-2在血管炎症和动脉粥样硬化形成中的作用进行研究。研究人员建立了一种缺乏系统PAR-2表达的脂蛋白E缺陷的小鼠（PAR-2-/-ApoE-/-）。还通过骨髓移植建立ApoE-/- 小鼠，缺乏或仅在骨髓（B

凝血系统与血管炎症密切相关，但其机制尚不明确。近期有研究表明蛋白酶激活受体（PAR）-2是激活因子X的主要受体，在血管细胞和白细胞中均有表达，提示PAR-2可能参与炎症病理过程。现研究人员对PAR-2在血管炎症和动脉粥样硬化形成中的作用进行研究。

研究人员建立了一种缺乏系统PAR-2表达的脂蛋白E缺陷的小鼠（PAR-2-/-ApoE-/-）。还通过骨髓移植建立ApoE-/- 小鼠，缺乏或仅在骨髓（BM）细胞中表达PAR-2。予以西式饮食喂养20周后，采用组织学分析、qPCR和Western blotting分析粥样硬化病损。并在体外采用BM来源的巨噬细胞来明确PAR-2的促炎症作用。此外，研究人员还在进行冠状动脉干预的患者中评估血浆激活因子X水平与冠状动脉粥样硬化的严重程度之间的相关性。

与ApoE-/-小鼠相比，PAR-2-/-ApoE-/-小鼠的动脉粥样硬化病损减少（p<0.05），伴随动脉粥样硬化斑块稳定，如脂质沉积(p<0.05)、胶原丢失(p<0.01)、巨噬细胞积累(p<0.05)以及炎症分子表达减少（p<0.05）。系统敲除ApoE-/-小鼠的PAR2可显著降低炎症分子在动脉中的表达水平。BM移植试验的结果显示造血细胞中的PAR-2可促进ApoE-/-小鼠的动脉粥样硬化。敲除PAR-2不影响代谢参数。体外试验显示激活因子X或PAR-2的特异性肽类激动剂可明显增加野生型小鼠BM来源的巨噬细胞（与PAR-2缺陷小鼠的相比）的炎症因子表达和脂质摄取。核因子κB信号激活参与PAR-2相关的血管炎症和巨噬细胞激活。在进行冠状动脉干预的人类中，血浆激活因子X的水平与冠状动脉粥样硬化的严重程度独立相关。

在ApoE-/-小鼠中，PAR-2信号激活巨噬细胞、促进血管严重，并可增加动脉粥样硬化。该信号或许也参与人类的动脉粥样硬化。

原始出处：

Tomoya Hara，et al.Protease-Activated Receptor-2 Plays a Critical Role in Vascular Inflammation and Atherosclerosis in Apolipoprotein E–Deficient Mice.Circulation.April 26，2018；138：1706–1719

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2019-08-24 ligang4439

#蛋白酶激活受体-2#

35 0
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2019-09-10 huangshifeng

#粥样硬化#

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2018-10-28 医者仁心

#蛋白酶#

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2018-10-26 shijzhiewnjhch

#血管炎#

27 0
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2018-10-26 ms6832696159214430

#血管炎症#

36 0
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2018-10-24 一个字-牛

学习了谢谢分享

74 0
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2018-10-24 kafei

学习了谢谢

79 0

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