Huang Xingxiao, Ping Yan, Sun Qiuli, Yu Mingjun, Yang Chao, Liu Xiao, Wang Long, Huang Jinyu
Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Cardiology, Westlake Laboratory of Life Sciences and Biomedicine, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.
Front Immunol. 2025 May 20;16:1591557. doi: 10.3389/fimmu.2025.1591557. eCollection 2025.
Percutaneous coronary intervention (PCI) remains the primary treatment for coronary artery disease (CAD), yet post-procedural arterial injury triggers cellular change and pathological inflammation, leading to thrombosis and restenosis. Recent studies have highlighted the chemokine CXCL2 play an important role in the immune response to tissue repair. However, the cellular mechanisms and the role of chemokine CXCL2 underlying arterial repair after PCI remain poorly understood.
Single-cell RNA sequencing (scRNA-seq) was used to characterize the heterogeneity and gene expression profiles of cells in a femoral artery injury (FAI) model. Animal models of FAI and cellular experiments were used to validate the effects of CXCL2 on smooth muscle cell proliferation.
(1) Mesenchymal stem cells (MSCs), smooth muscle cells (SMCs), and macrophages play pivotal roles in arterial repair. And distinct subpopulations within these cell types were identified, each exhibiting unique functional characteristics and temporal dynamics during repair. (2) Notably, we identified an inflammatory SMC subpopulation (SMC2) that actively secretes chemokine CXCL2, which promotes SMC proliferation and mediates arterial remodeling after injury, suggesting its potential as a therapeutic target.
This study provides a comprehensive cell atlas of the injured artery, offering valuable insights into the complex cellular interactions, signaling pathways and immune responses involved in orchestrating vascular repair. Our findings show chemokine CXCL2 as a key mediator of SMC proliferation and provide a roadmap for developing CXCL2-targeted therapies to improve vascular outcomes in PCI patients.
经皮冠状动脉介入治疗（PCI）仍然是冠状动脉疾病（CAD）的主要治疗方法，然而术后动脉损伤会引发细胞变化和病理性炎症，导致血栓形成和再狭窄。最近的研究强调趋化因子CXCL2在组织修复的免疫反应中起重要作用。然而，PCI术后动脉修复过程中趋化因子CXCL2的细胞机制和作用仍知之甚少。
采用单细胞RNA测序（scRNA-seq）对股动脉损伤（FAI）模型中的细胞异质性和基因表达谱进行表征。利用FAI动物模型和细胞实验验证CXCL2对平滑肌细胞增殖的影响。
（1）间充质干细胞（MSCs）、平滑肌细胞（SMCs）和巨噬细胞在动脉修复中起关键作用。在这些细胞类型中鉴定出不同的亚群，每个亚群在修复过程中表现出独特的功能特征和时间动态。（2）值得注意的是，我们鉴定出一种炎症性SMC亚群（SMC2），它能主动分泌趋化因子CXCL2，促进SMC增殖并介导损伤后动脉重塑，提示其作为治疗靶点的潜力。
本研究提供了损伤动脉的综合细胞图谱，为协调血管修复所涉及的复杂细胞相互作用、信号通路和免疫反应提供了有价值的见解。我们的研究结果表明趋化因子CXCL2是SMC增殖的关键介质，并为开发以CXCL2为靶点的疗法以改善PCI患者的血管结局提供了路线图。
