蛋白酶激活受体-2 在无脂蛋白E缺陷小鼠的血管炎症和动脉样硬化中起着关键作用
Tomoya Hara1, Pham Tran Phuong1, Daiju Fukuda1,2
1Departments of Cardiovascular Medicine (T.H., P.T.P., D.F., K.Y., S.N., S.Y., K.K., H.Y., T.S., T.W., M.Sata), Tokushima University Graduate School of Biomedical Sciences, Japan.
Circulation
|April 28, 2018
概括
蛋白酶激活受体-2 (PAR-2) 信号通过激活巨细胞促进血管炎症和动脉样硬化. 抑制PAR-2可能是预防心血管疾病的治疗策略.
科学领域:
- 心血管生物学
- 炎症研究
- 动脉样硬化的发病
背景情况:
- 凝血系统和血管炎症是相关的,但机制尚不清楚.
- 蛋白酶激活受体-2 (PAR-2) 是激活X因子的受体,存在于血管细胞和白细胞中.
- 在炎症性疾病的发病过程中涉及PAR-2,并可能在动脉样硬化中发挥作用.
研究的目的:
- 研究PAR-2在血管炎症和动脉生成中的作用.
- 确定PAR-2信号是否有助于动脉样硬化斑块的发展.
- 探索针对心血管疾病治疗PAR-2的潜力.
主要方法:
- 产生了缺乏PAR-2的阿波利波蛋白E (ApoE-/-) 的小鼠 (PAR-2-/- ApoE-/).
- 使用骨髓移植研究血液细胞中的PAR-2表达.
- 分析了动脉样硬化病变,炎症标志物和脂质沉积通过组织学,qPCR和西式涂抹.
- 用骨髓衍生的巨细胞进行了体外实验,以评估PAR-2功能.
- 研究了人体血激活X因子水平与冠状动脉硬化严重程度之间的相关性.
主要成果:
- 与ApoE-/-小鼠相比,PAR-2-/- ApoE-/-小鼠的动脉样损伤和斑块稳定性有所减少.
- 系统性PAR-2删除降低了大动脉中的炎症分子表达.
- 在造血细胞中PAR-2被证明有助于动脉生成.
- 实验室研究证实PAR-2激活会增加巨细胞中的炎症分子表达和脂质吸收.
- 在人类中,激活的X因子水平与冠状动脉硬化严重程度独立相关.
结论:
- 在ApoE/-小鼠中,PAR-2信号激活巨细胞并促进血管炎症,加剧动脉样硬化.
- 该PAR-2途径是人类动脉生成的潜在贡献者.
- 针对PAR-2可能是心血管疾病的新疗法.
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