单细胞转录组学分析揭示了冠状动脉易损斑块外周血T细胞血小板聚集的诊断。

摘要(中文译文)

由易损斑块（VP）不稳定引起的急性冠状动脉综合征是心血管死亡的主要原因。目前对VP的诊断方法受到侵入性或低特异性的限制，这突显了对非侵入性生物标志物的需求。我们使用来自冠状动脉疾病（CAD）患者和对照组的外周血单核细胞（PBMCs）的单细胞RNA测序（scRNA-seq），鉴定出VP患者中显著富集的循环T细胞血小板聚集物（TPAs），并通过促炎途径与斑块不稳定相关联。通过高维加权基因共表达网络分析，我们发现了TPAs的中心基因，并证明了它们在斑块失稳中的作用。此外，利用机器学习，包括Boruta、最小绝对收缩和选择算子（LASSO）回归和支持向量机递归特征消除（SVM-RFE），我们筛选了五种可以作为VP诊断指标的血液生物标志物。我们的研究表明，TPAs在VP的形成中起着关键作用。此外，我们确定EPHB6、STAT1、RPL23、IKZF3和AHCY是无创检测VPs的潜在循环生物标志物。

Abstract

Acute coronary syndrome, driven by vulnerable plaque (VP) instability, is a major cause of cardiovascular mortality. Current diagnostic methods for VPs are limited by invasiveness or low specificity, highlighting the need for non-invasive biomarkers. Using single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from coronary artery disease (CAD) patients with VPs and controls, we identified circulating T cell-platelet aggregates (TPAs) significantly enriched in VP patients and linked to plaque instability via pro-inflammatory pathways. Through high dimensional weighted gene co-expression network analysis, we discovered TPAs' hub genes and demonstrated their role in plaque destabilization. Furthermore, employing machine learning, including Boruta, least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE), we screened for five blood biomarkers that can serve as diagnostic indicators for VPs. Our study demonstrates that TPAs are critically involved in VPs formation. Furthermore, we identified EPHB6, STAT1, RPL23, IKZF3 and AHCY as potential circulating biomarkers for non-invasive detection of VPs.

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