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通过与肝硫酸蛋白糖结合,APRIL可以抑制动脉样硬化
Dimitrios Tsiantoulas1, Mahya Eslami2, Georg Obermayer3,4
1Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria. dimitris.tsiantoulas@meduniwien.ac.at.
Nature
|August 26, 2021
概括
一种诱导增殖的配体 (APRIL) 通过与肝素硫酸蛋白质结合来预防动脉样硬化,从而减少LDL的保留和炎症. 这一发现为预防心血管疾病提供了新的见解.
科学领域:
- 心血管生物学
- 免疫学
- 蛋白质糖研究
背景情况:
- 动脉样性心血管疾病是全球主要的死亡原因,
- 低密度脂蛋白 (LDL) 在动脉中被困,导致斑块形成,导致炎症.
- 在此过程中A增殖诱导配体 (APRIL) 的作用尚不清楚.
研究的目的:
- 研究APRIL在动脉样硬化的作用.
- 阐明APRIL影响动脉硬化斑块形成的机制.
- 探索APRIL作为心血管疾病治疗点的潜力.
主要方法:
- 在动脉硬化小鼠模型中,APRIL的基因切除和抗体介导的耗尽.
- 在动脉样硬化斑块中分析LDL保留,巨细胞积累和死核形成.
- 研究APRIL与肝酸硫酸蛋白糖 (HSPG),特别是HSPG2的相互作用.
- 对血清非正规APRIL (nc-APRIL) 度及其与心血管死亡率的评估.
主要成果:
- 在小鼠中,APRIL缺乏或耗尽可加剧动脉样硬化.
- 通过与HSPG2结合,APRIL可以预防动脉样硬化,限制LDL的保留和巨细胞的积累.
- 肝素硫酸盐缺乏HSPG2的小鼠没有显示APRIL耗尽对动脉样硬化的影响.
- 用抗APRIL抗体治疗可以减少实验性动脉样硬化.
- 血清nc-APRIL水平与患者的长期心血管死亡有关.
结论:
- 通过通过HSPG2调节LDL保留和炎症,APRIL在动脉样硬化中起着保护作用.
- 针对APRIL,特别是HSPG结合形式,可能为心血管疾病提供一种新的治疗策略.
- 非正规的APRIL (nc-APRIL) 作为一种潜在的心血管风险生物标志物.
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