人类动脉样硬化斑块中的膜类型1矩阵金属蛋白酶表达:有证据表明由促炎媒介激活
T B Rajavashisth1, X P Xu, S Jovinge
1Atherosclerosis Research Center, Burns and Allen Research Institute, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. rajavashisth@cshs.org
Circulation
|June 22, 1999
概括
矩阵金属蛋白酶1 (MT1-MMP) 存在于动脉样硬化斑块中,由光滑肌细胞和巨细胞表达. 促炎分子增加MT1-MMP表达,可能影响动脉样硬化中的细胞外基质重塑.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 生物化学 生物化学
背景情况:
- 矩阵金属蛋白酶 (MMPs) 参与动脉样硬化斑块的重塑和破坏.
- 膜型1MMP (MT1-MMP) 是一种激活亲MMP-2的跨膜MMP.
- 人类动脉样硬化斑块中MT1-MMP的作用以及由炎症因素对其调节的作用尚未完全理解.
研究的目的:
- 为了研究MT1-MMP在人类动脉样硬化斑块中的表达.
- 为了确定促炎分子是否调节血管细胞中的MT1-MMP表达.
主要方法:
- 免疫细胞化学被用来检查人类动脉中的MT1-MMP表达.
- 北方斑块,核糖核酶保护测定,西部斑块,免疫沉和凝组图被用来评估MT1-MMP mRNA,蛋白质和培养的光滑肌肉细胞 (SMC) 中的活性.
- 流细胞计用于评估巨细胞 (Mphi) 中的MT1-MMP表达.
主要成果:
- MT1-MMP表达在正常血管的中间SMC和动脉样硬化斑块内,与SMC和Mphi.同定位.
- 培养的SMC构成性表达MT1-MMP,暴露于IL-1alpha,TNF-alpha和氧化LDL (ox-LDL) 后,mRNA和蛋白质增加2至4倍.
- 在TNF-α刺激后,人类单细胞衍生的Mphi显示MT1-MMP表达增加.
结论:
- 人类动脉样硬化斑块内的SMC和Mphi表达MT1-MMP.
- 促炎分子显著上调血管SMC和Mphi中的MT1-MMP表达.
- 炎症媒介对MT1-MMP的调节可能在动脉样硬化期间在细胞外基质重塑中发挥作用.
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