动脉样硬化中的免疫调节和失硫症会影响疾病的进展和治疗
Wei Lu1, Zhidong Zhang1, Gang Qiao1
1Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou 451460, China.
Biomedicines
|April 29, 2025
概括
这项研究揭示了动脉样硬化中的二硫化,确定了Cathepsin C (CTSC) 作为一种治疗标,通过减少光滑肌肉细胞亡来稳定斑块. 一个新的风险评分有助于识别高风险患者.
科学领域:
- 心血管生物学 心血管生物学
- 分子病理学分子病理学
- 生物信息学是一种生物信息学.
背景情况:
- 动脉样硬化是一种复杂的血管疾病,分子机制不明.
- 细胞异质性,代谢失调和慢性炎症是其关键特征.
- 现有研究尚未完全阐明导致动脉样硬化进展的复杂途径.
研究的目的:
- 在动脉样硬化斑块中综合地绘制免疫细胞相互作用和细胞异质性,使用scRNA-seq.
- 研究光滑肌细胞 (SMC) 的作用,并确定动脉样硬化的主要生物标志物.
- 为高风险患者开发和验证诊断风险评分模型.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 用于免疫细胞映射和SMC异质性分析.
- 伪实时轨迹分析以了解SMC激活路径.
- 综合生物信息学 (WGCNA,机器学习) 用于识别生物标志物 (CTSC,TGFBI,GMFG) 并开发风险评分模型.
- 在体外和体内实验,以评估CTSC的功能作用.
主要成果:
- SMCs是占主导地位的细胞类型,表现出高的二硫化密度和动态激活通路.
- 观察到巨细胞和SMC之间的细胞间通信,在斑块区域具有特定的信号.
- 综合CTSC,TGFBI和GMFG的诊断风险评分准确识别了高风险患者.
- 在实验室中,CTSC敲除增强了SMC存活率和减少了亡;在体内研究显示,减少了斑块负担.
结论:
- 不硫化症在动脉样硬化发展中起着重要作用.
- 通过抑制SMC亡和氧化损伤,CTSC是稳定斑块的潜在治疗标.
- 开发的风险评分模型是患者分层和精确治疗的宝贵工具.
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