斑块侵蚀风险和JAK2 V617F变种的发生
Shengfang Wang1,2,3, Xing Luo1,3, Sining Hu1,3
1Department of Cardiology of the Second Affiliated Hospital, Harbin Medical University, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), No. 246 Xuefu Road, Nangang District, Harbin 150001, China.
具有JAK2 V617F突变的克隆性血液形成显著增加了心肌梗塞风险,特别是斑块侵蚀. 增强的中性粒细胞激活可能会推动这种关联.
科学领域:
- 心血管医学 心血管医学
- 血液学 血液学 血液学
- 遗传学 遗传学 是一个
背景情况:
- 不确定潜力的克隆性血液形成 (CHIP) 与心肌梗塞 (MI) 风险增加有关.
- 在CHIP内部的JAK2 V617F突变大大增加了心脏病发作风险.
- 连接JAK2 V617F与MI亚型,斑块侵蚀和破裂的特定机制尚不清楚.
研究的目的:
- 研究JAK2 V617F突变与心肌梗塞 (MI) 的机制之间的关联,特别是斑块侵蚀和斑块破裂.
- 探索中性粒细胞激活在JAK2 V617F和MI侵蚀之间的联系中的潜在作用.
主要方法:
- 病例控制研究涉及728例侵蚀病例,919例破裂病例和804例对照.
- 数字滴聚合酶连锁反应 (PCR) 用于检测JAK2 V617F.
- 在来自JAK2 V617F载体和健康捐赠者的中性粒细胞上进行单细胞RNA测序.
主要成果:
- JAK2 V617F载体 (VAF ≥1%) 在侵蚀患者中明显更为普遍 (3.57%),与破裂患者 (.76%) 和对照患者 (.37%) 相比.
- 后勤回归显示了JAK2 V617F与侵蚀 (OR 16.246,P < .0001) 之间的强烈关联,但没有破裂 (OR 1.677,P = .495).
- 来自JAK2 V617F载体的中性粒细胞表现出与激活,粘附,迁移和颗粒分泌相关的基因的高度表达.
结论:
- 由于斑块侵蚀,JAK2 V617F与心肌梗塞风险增加显著相关.
- 在JAK2 V617F载体中增强的中性粒细胞激活可能是导致斑块侵蚀和随后的MI的关键机制.
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