在心肌梗塞中免疫检查点TIM-3/HMGB-1轴
Laura I Yousif1, Aukje G Sijtema1, Ymke Appels1
1Erasmus MC, Cardiovascular Institute, Thorax Center, Department of Cardiology, Rotterdam, The Netherlands.
NPJ cardiovascular health
|September 22, 2025
概括
TIM-3通路,特别是它与HMGB-1的相互作用,在心肌梗塞 (MI) 后的心脏炎症中起着至关重要的作用. 准这种途径可能为心血管疾病提供新的治疗策略.
科学领域:
- 心血管免疫学心血管免疫学
- 心血管疾病的分子机制
背景情况:
- 免疫检查点在心血管疾病中尚不清楚.
- 在心肌梗塞 (MI) 中TIM-3通路的作用在很大程度上是未被探索的.
研究的目的:
- 在人血清,外周血液单核细胞 (PBMC) 和心脏组织中研究TIM-3通路.
- 探索TIM-3/HMGB-1相互作用作为潜在的治疗点心脏炎症后MI.
主要方法:
- 在357名心脏病后患者的血清中分析TIM-3连接体 (甲状腺素-9,HMGB-1).
- 来自38名心脏病患者和38名对照组的PBMC单细胞RNA测序.
- 单核RNA测序和心肌梗塞患者心脏组织的空间转录组学.
- 在体外巨细胞刺激测定中使用HMGB-1和TIM-3阻断.
主要成果:
- 血清中的TIM-3连接体与心脏重塑后MI相关.
- 在淋巴细胞中观察到急性TIM-3下调,后来在MI后的髓状细胞中观察到.
- 在心肌细胞和心脏梗塞组织中提高HMGB-1的调节,与髓质TIM-3相互作用.
- 促炎性巨细胞表现出TIM-3表达和NLRP3炎症酶活性.
- 刺激HMGB-1诱导了促炎性巨细胞两极分化,被TIM-3抑制阻断.
结论:
- TIM-3/HMGB-1轴与心肌梗塞后的心脏炎症有关.
- TIM-3/HMGB-1相互作用代表了管理心脏发作后心脏炎症的潜在治疗标.
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