整合多模式的omics来识别冠状动脉心脏病治疗性动脉样硬化途径
Sophie C de Ruiter1, Marion van Vugt2, Chris Finan3
1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
EBioMedicine
|October 16, 2025
概括
这项研究将尿道代谢分解产品与冠心病 (CHD) 风险联系起来,确定氨基酸代谢是关键途径. 这些发现突出了动脉样硬化斑块中的16种蛋白质,用于在心血管疾病中开发潜在的药物.
科学领域:
- 生物医学科学 生物医学科学
- 遗传学 是一个遗传学.
- 代谢学 代谢学 代谢学
背景情况:
- 尿道代谢分解产物可以表明动脉样硬化相关组织的代谢变化.
- 这些产品可能为冠心病 (CHD) 提供治疗点.
研究的目的:
- 整合多omics数据 (尿中代谢物,血蛋白,斑块组织,单细胞表达) 以找到可用药物的代谢途径用于心脏病.
- 确定冠状动脉心脏病 (CHD) 的新疗法.
主要方法:
- 在尿路代谢物,蛋白质和心血管疾病病例的全基因组关联研究中利用门德尔的随机化.
- 使用来自Athero-Express生物库的表达数据,将血蛋白与斑块脆弱性联系起来.
- 分析了来自动脉斑块的单细胞RNA测序数据,以评估不同细胞类型中的蛋白质表达.
主要成果:
- 确定了29种与心脏病相关的尿道代谢分解产物,主要来自氨基酸代谢.
- 发现了113种血蛋白与尿路代谢物和心血管疾病的协同关联.
- 在动脉样硬化斑块中发现了16种与斑块脆弱性相关的蛋白质,包括已知的药物标 (IL6R,AT1B2) 和重新定位候选物 (C1S).
结论:
- 氨基酸代谢是导致冠心病 (CHD) 风险的重要途径.
- 突出显示了与心血管疾病相关的动脉样硬化斑块内的16种优先级蛋白质.
- 为开发新治疗策略提供了关键的见解.
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