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干联素-18抑制在Jak2V617F 克隆性血液形成中加剧动脉样硬化
Mojdeh Tavallaie1, Cheng-Chieh Hsu1, Brian D Hardaway1
1Division of Molecular Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.
JACC. Basic to translational science
|February 26, 2026
概括
矛盾的是,JAK2V617F 克隆性血液形成中的介质素-18 (IL-18) 抑制通过促进缩和病变生长而使动脉样硬化恶化,挑战目前的治疗假设.
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
- 血液学 血液学 血液学
背景情况:
- 由JAK2V617F驱动的克隆造血 (CH) 通过炎症酶激活和细胞因子释放加速动脉样硬化.
- 介质蛋白-18 (IL-18) 在这个过程中的特定作用仍然不完全理解.
研究的目的:
- 在JAK2V617F驱动的CH.的背景下,研究IL-18对动脉样硬化进展的确切贡献.
- 阐明IL-18影响动脉样硬化斑块发育和稳定的分子机制.
主要方法:
- 使用了JAK2V617FCH小鼠模型.
- 用于抑制IL-18.8的抗体.
- 分析了动脉样硬化斑块的特征,包括原蛋白含量,病变大小和死核形成.
- 评估了炎症酶激活,细胞死亡途径 (细胞亡与亡),细胞增生和干扰素马信号传递.
主要成果:
- IL-18阻断增加了斑块原蛋白含量,但矛盾的是,促进了早期的病变生长和先进的死核形成.
- 抑制IL-18逆转,在黑色素瘤2炎症酶激活中缺席,但将细胞死亡转移到细胞亡.
- 观察到受损的乙细胞形成和干扰素马信号的减少,导致亡的增加和增强的原沉积.
结论:
- 与普遍假设相反,IL-18抑制不会稳定JAK2V617FCH中的动脉样斑块.
- 减少IL-18信号破坏了炎症细胞的活性,改变了免疫细胞的功能,最终促进了斑块的脆弱性.
- 这些发现突出了炎症细胞生物学,适应性免疫和动脉样硬化斑块稳定性之间的复杂相互作用.
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