从炎症角度鉴定冠状动脉样硬化潜在治疗点,通过综合蛋白质学和单细胞蛋白质学
Hesong Wang1, Fengzhe Xie2, Meng Wang1
1Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150081, China.
International journal of molecular sciences
|July 12, 2025
概括
这项研究确定了11种与冠状动脉样硬化 (CAS) 有因果关系的炎症蛋白. 三个有希望的目标,CELSR2,FN1和SPARCL1,显示出开发用于心血管疾病的新抗炎疗法的潜力.
科学领域:
- 心血管遗传学 心血管遗传学
- 蛋白质组学是指蛋白质组学.
- 炎症生物学 炎症生物学
背景情况:
- 冠状动脉样硬化 (CAS) 是全球心血管疾病的主要原因之一.
- 了解CAS已经发展,认识到炎症是关键驱动因素,需要确定新的治疗点.
- 抗炎症策略在治疗动脉样硬化方面越来越重要.
研究的目的:
- 使用全蛋白质组门德尔随机化 (MR) 方法识别冠状动脉样硬化 (CAS) 的新型炎症相关蛋白标.
- 验证因果关系并探索已识别的蛋白质的治疗潜力.
- 研究候选蛋白质的表达模式和药物可用性.
主要方法:
- 整个蛋白质组的门德尔随机化 (MR) 分析整合了来自英国PPP,冰岛和FinnGen队伍的大规模蛋白质组学和CAS结果数据.
- 复制MR使用多个蛋白质组和CAS数据集的元分析.
- 局部化,反向MR和SMR分析,以获得可靠的因果推断.
- 单细胞RNA-seq用于血管细胞中的基因表达分析.
- 对已识别的蛋白质标进行药效评估.
主要成果:
- 整个蛋白质组的MR确定了11种与CAS显著相关的蛋白质 (p <3.52 × 10^-5),其中大多数与心血管疾病风险有关.
- 局部化分析证实了CAS中PCSK9,IL6R,CELSR2,FN1和SPARCL1的因果作用.
- 五个基因 (TGFB1,SPARCL1,IL6R,FN1,CELSR2) 在冠状动脉斑块或健康血管系统的光滑肌细胞中显示出特定的表达.
- CELSR2,FN1和SPARCL1成为有前途的治疗点,FN1和TGFB1被确定为潜在的药物重用.
结论:
- 这项研究为11种与炎症相关的蛋白质提供了强有力的证据,这些蛋白质与冠状动脉样硬化因果相关.
- CELSR2,FN1和SPARCL1代表了新型抗动脉样硬化治疗的有希望的治疗点.
- 这些发现支持针对CAS开发有针对性的抗炎疗法,有潜在的药物重用.
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