脂蛋白 (a) 诱导人体巨细胞中的卡斯帕酶-1激活和IL-1信号传递
Martina B Lorey1,2, Amer Youssef3, Lauri Äikäs1
1Atherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland.
Frontiers in cardiovascular medicine
|June 9, 2023
概括
升高的脂蛋白 (Lp) 驱动炎症和动脉样硬化. 这项研究揭示了Lp(a) 激活了巨细胞中的caspase-1和IL-1信号,与LDL不同,由于其独特的分子组成.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 分子医学是分子医学.
背景情况:
- 升高的脂蛋白 (Lp) 是动脉样硬化的一个重要危险因素.
- 对于Lp (a) 的确切的促炎机制仍然不完全理解.
研究的目的:
- 为了研究Lp (a) 对人类巨细胞的异质炎症作用.
- 为了比较Lp (a) 与低密度脂蛋白 (LDL) 和阿波脂蛋白 (apo) 的炎症潜力.
主要方法:
- 用Lp(a) 或重组Apo(a) 治疗的THP-1巨细胞的RNA测序.
- 用含有不同Lp(a) 水平的血清刺激THP-1巨细胞.
- 在初级和THP-1衍生巨细胞中对Lp (a),LDL和复合性apo (a) 的比较分析.
- 对Lp (a) 和LDL颗粒的蛋白质和脂质分析.
主要成果:
- (a) 在巨细胞中强烈诱导剂量依赖的酶-1激活和IL-1β和IL-18的分泌.
- 再组合的apo (a) 在THP-1细胞中显示出强效,但在初级巨细胞中反应较弱.
- Lp (a) 颗粒表现出一种有氧炎性蛋白质和脂质,缺乏多不和脂肪酸和高的n-6/n-3比率.
结论:
- Lp (a) 直接促进炎症基因表达,并激活巨细胞中的-1/IL-1信号传递.
- 与LDL相比,Lp(a) 的独特分子概况是其高度的异质炎症潜力的基础.
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