在脂蛋白上氧化脂 (a) 引起动脉壁炎症和人类的炎症单细胞反应
Fleur M van der Valk1, Siroon Bekkering1, Jeffrey Kroon1
1From Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
升高的脂蛋白 (Lp) 通过增加动脉炎症和单细胞流通导致心血管疾病. 它的氧化脂 (OxPLs) 调解这些促炎作用,提供了一个新的治疗点.
科学领域:
- 心血管医学
- 免疫学
- 分子生物学
背景情况:
- 高脂蛋白 (Lp) 是一个重要的心血管风险因素.
- 在Lp (a) 致病性背后的机制尚未完全理解.
- Lp (a) 含有促炎性氧化脂 (OxPL),这表明它可能在动脉血中起作用.
研究的目的:
- 研究Lp (a) 导致心血管疾病的机制.
- 确定OxPLs在Lp (a) 中介致病性中的作用.
- 评估Lp (a) 对单细胞功能和动脉炎症的影响.
主要方法:
- 在体内成像 (MRI,PET/CT,SPECT/CT) 以评估动脉样硬化负担和炎症.
- 活体单细胞分析 (FACS,迁移试验,刺激试验).
- 使用受过训练的免疫模型进行体外研究,以调查Lp-a) -单细胞相互作用.
主要成果:
- 患有升高Lp (a) 的患者表现出动脉炎症和单细胞流通的增加.
- 来自高Lp(a) 个体的单细胞表现出原始状态,增加了迁移和细胞因子的产生.
- 在体外,Lp增加了单细胞的炎症反应,这种效果取决于其OxPL含量.
结论:
- 促使单细胞向动脉壁进行招募.
- Lp (a) 的OxPL含量对于调解炎症反应至关重要.
- 这些发现阐明了Lp (a) 诱导的心血管疾病的新机制.
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