Background The maximum aortic diameter remains the diagnostic criteria and the indicator for prognosis prediction of abdominal aortic aneurysms (AAA). An additional imaging modality is currently needed to help evaluate the prognosis of AAA as well as early detection of AAA formation. This study evaluated the most effective inflammatory markers for AAA using single-cell sequencing and, from these, developed probes to facilitate in vivo multimodal imaging of AAA inflammation. Methods and Results Single-cell RNA sequencing (scRNAseq) of the human aortic aneurysms, GSE155468 and GSE166676 datasets, identified CXCR4 as the most representative marker. Anti-CXCR4-PE antibody was conjugated to superparamagnetic iron oxide nanoparticles to synthesise Fe3O4-anti-CXCR4-PE probes. The biocompatibility and specificity of the probes were validated in vivo and in vitro. Magnetic particle imaging (MPI) and fluorescence imaging (FLI) were performed to assess inflammation in early and advanced AAA mouse models. CXCR4-specific receptor inhibitor, AMD3100, was used for confirming CXCR4 as an excellent target for AAA imaging and therapy. scRNAseq indicated that chemokine-related pathways were upregulated in aortic aneurysms, and CXCR4 was the chemokine receptor that markers all AAA-related immune cells and inflammatory vascular cells. Fe3O4-anti-CXCR4-PE effectively recognised immune cells and inflammatory vascular cells, as strong MPI and FLI signals corresponded to increased CXCR4, CD45, and CD68 levels which represented AAA severity and rupture risk. Importantly, Fe3O4-anti-CXCR4-PE can help identify early AAA formation when ultrasound is undiagnosable. Finally, AMD3100 treatment in AAA mouse model inhibited AAA expansion and rupture and reduced aortic wall inflammation by inhibiting accumulation of immune cells and hematopoietic stem cells. Conclusion CXCR4 markers immune cells and inflammatory vascular cells in AAA and is associated with AAA prognosis in a mouse model of AAA. CXCR4-targeting multimodal MPI/FLI provides a novel approach for AAA prognosis prediction and early detection.

中文翻译：

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CXCR4 靶向灵敏磁颗粒显像用于腹主动脉瘤的早期检测和预后评估，通过识别总炎细胞


背景 最大主动脉直径仍然是腹主动脉瘤 （AAA） 的诊断标准和预后预测指标。目前需要一种额外的影像学检查方法来帮助评估 AAA 的预后以及 AAA 形成的早期检测。本研究使用单细胞测序评估了 AAA 最有效的炎症标志物，并从中开发了探针以促进 AAA 炎症的体内多模式成像。方法和结果 人主动脉瘤单细胞 RNA 测序 （scRNAseq），GSE155468 和 GSE166676 数据集，确定 CXCR4 是最具代表性的标志物。将抗 CXCR4-PE 抗体与超顺磁性氧化铁纳米颗粒偶联，合成 Fe3O4-抗 CXCR4-PE 探针。探针的生物相容性和特异性在体内和体外进行了验证。进行磁粒子成像 （MPI） 和荧光成像 （FLI） 以评估早期和晚期 AAA 小鼠模型的炎症。CXCR4 特异性受体抑制剂 AMD3100 用于确认 CXCR4 是 AAA 成像和治疗的优秀靶点。scRNAseq 表明，在主动脉瘤中趋化因子相关通路上调，CXCR4 是标记所有 AAA 相关免疫细胞和炎性血管细胞的趋化因子受体。Fe3O4-anti-CXCR4-PE 有效识别免疫细胞和炎性血管细胞，因为强 MPI 和 FLI 信号对应于 CXCR4、CD45 和 CD68 水平升高，代表 AAA 严重程度和破裂风险。重要的是，Fe3O4 抗 CXCR4-PE 可以帮助在超声无法诊断时识别早期 AAA 的形成。 最后，AAA 小鼠模型中的 AMD3100 处理通过抑制免疫细胞和造血干细胞的积累来抑制 AAA 的扩增和破裂并减少主动脉壁炎症。结论 CXCR4 在 AAA 小鼠模型中标记免疫细胞和炎性血管细胞，并与 AAA 小鼠模型的 AAA 预后相关。靶向 CXCR4 的多模态 MPI/FLI 为 AAA 预后预测和早期检测提供了一种新方法。