Cao Genmao, Zhang Ruijing, Jia Xiaohua, Jiang Bo, Li Yaling, Xuan Xuezhen, Tian Jie, Hui Hui, Xin Shijie, Dong Honglin
Department of Vascular Surgery, 2nd Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan 030001, China.
Department of Nephrology, 2nd Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan, China.
Cardiovasc Res. 2025 Apr 22;121(2):324-338. doi: 10.1093/cvr/cvae255.
The maximum aortic diameter remains the diagnostic criteria and the indicator for prognosis prediction of abdominal aortic aneurysms (AAAs). 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.
Single-cell RNA sequencing (scRNAseq) of the human aortic aneurysms, GSE155468 and GSE166676 data sets, identified CXCR4 as the most representative marker. Anti-CXCR4-PE antibody was conjugated to superparamagnetic iron oxide nanoparticles to synthesize 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 marks all AAA-related immune cells and inflammatory vascular cells. Fe3O4-anti-CXCR4-PE effectively recognized immune cells and inflammatory vascular cells, as strong MPI and FLI signals corresponded to increased CXCR4, CD45, and CD68 levels that 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 haematopoietic stem cells.
CXCR4 marks 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.
最大主动脉直径仍是腹主动脉瘤（AAA）的诊断标准及预后预测指标。目前需要一种额外的成像方式来帮助评估AAA的预后以及早期检测AAA的形成。本研究使用单细胞测序评估了用于AAA的最有效的炎症标志物，并据此开发了探针以促进AAA炎症的体内多模态成像。
对人类主动脉瘤的GSE155468和GSE166676数据集进行单细胞RNA测序（scRNAseq），确定CXCR4为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。在体内和体外验证了探针的生物相容性和特异性。对早期和晚期AAA小鼠模型进行磁粒子成像（MPI）和荧光成像（FLI）以评估炎症。使用CXCR4特异性受体抑制剂AMD3100来确认CXCR4是AAA成像和治疗的理想靶点。scRNAseq表明趋化因子相关通路在主动脉瘤中上调，CXCR4是标记所有与AAA相关的免疫细胞和炎性血管细胞的趋化因子受体。Fe3O4-抗CXCR4-PE有效识别免疫细胞和炎性血管细胞，因为强烈的MPI和FLI信号对应于代表AAA严重程度和破裂风险的CXCR4、CD45和CD68水平的升高。重要的是，当超声无法诊断时，Fe3O4-抗CXCR4-PE有助于识别早期AAA的形成。最后，在AAA小鼠模型中进行AMD3100治疗可抑制AAA的扩张和破裂，并通过抑制免疫细胞和造血干细胞的积聚来减轻主动脉壁炎症。
CXCR4标记AAA中的免疫细胞和炎性血管细胞，并与AAA小鼠模型的预后相关。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。
