Key Laboratory for Experimental Teratology of the Ministry of Education and Research Center for Experimental Nuclear Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Radiology Department, Qilu Hospital of Shandong University, Jinan, China.
J Cell Mol Med. 2022 Apr;26(8):2152-2162. doi: 10.1111/jcmm.17237. Epub 2022 Feb 15.
Noninvasive imaging atherosclerotic (AS) plaque is of great importance for early diagnosis. Recently, CD93 in MΦ was linked to atherosclerosis development. Herein, we have investigated whether CD93 in MΦ is a potential novel target for atherosclerotic plaque imaging. CD93 and CD93 MΦ were prepared with or without LPS stimulation, before biological activity was evaluated. A rat AS model was produced with left carotid artery clamped. Whole-body/ex vivo phosphor autoradiography of the artery and biodistribution were investigated after incorporation of H-2-DG into CD93 and CD93 MΦ or after I-α-CD93 ( I-anti-CD93mAb) injection. The plaque tissue was subjected to CD93/CD68 immunofluorescence/immunohistochemistry staining. CD93 and CD93 MΦ cells were successfully prepared without significant effect on bioactivity after incorporative labelled with H-2-DG. The AS model was successfully established. Biodistribution studies showed that adoptive transfer of H-2-DG-CD93 MΦ or I- α-CD93 injection resulted in accumulation of radioactivity within the atherosclerotic plaque in the clamped left carotid artery. T/NT (target/non-target, left/right carotid artery) ratio was higher in the H-2-DG-CD93 MΦ adoptive transfer group than in the H-2-DG-CD93 MΦ group (p < .05). Plaque radioactivity in the I-α-CD93 injection group was significantly higher than in the I-IgG control group (p < .01). The higher radioactivity accumulated in the clamped left carotid artery was confirmed by phosphor autoradiography. More importantly, CD93/CD68 double-positive MΦ accumulated at the atherosclerotic plaque in H-2-DG-CD93 MΦ adoptive transfer group, which correlated with plaque radioactivity (r = .99, p < .01). In summary, both adoptive-transferred H-2-DG-labelled CD93 MΦ and I-α-CD93 injection specifically targeted CD93 in atherosclerotic plaque. CD93 is a potential target in atherosclerotic plaque imaging.
非侵入性成像动脉粥样硬化(AS)斑块对于早期诊断非常重要。最近,巨噬细胞中的 CD93 与动脉粥样硬化的发展有关。在此,我们研究了巨噬细胞中的 CD93 是否是动脉粥样硬化斑块成像的潜在新靶点。用或不用 LPS 刺激制备 CD93 和 CD93 巨噬细胞,然后评估其生物学活性。用左颈动脉夹闭制备大鼠 AS 模型。将 H-2-DG 掺入 CD93 和 CD93 巨噬细胞后,或注射 I-α-CD93(I-抗 CD93mAb)后,进行动脉的全身/体外磷放射性自显影和生物分布研究。对斑块组织进行 CD93/CD68 免疫荧光/免疫组织化学染色。成功制备了 CD93 和 CD93 巨噬细胞细胞,在掺入 H-2-DG 后对其生物活性没有显著影响。成功建立了 AS 模型。生物分布研究表明,H-2-DG-CD93 巨噬细胞的过继转移或 I-α-CD93 注射导致放射性物质在夹闭的左颈动脉中的动脉粥样硬化斑块内积聚。与 H-2-DG-CD93 巨噬细胞组相比,H-2-DG-CD93 巨噬细胞过继转移组的 T/NT(靶/非靶,左/右颈动脉)比值更高(p <.05)。与 I-IgG 对照组相比,I-α-CD93 注射组的斑块放射性显著更高(p <.01)。磷放射性自显影证实,夹闭的左颈动脉中积聚了更高的放射性。更重要的是,在 H-2-DG-CD93 巨噬细胞过继转移组中,CD93/CD68 双阳性巨噬细胞在动脉粥样硬化斑块中积聚,与斑块放射性相关(r =.99,p <.01)。总之,过继转移的 H-2-DG 标记的 CD93 巨噬细胞和 I-α-CD93 注射均可特异性靶向动脉粥样硬化斑块中的 CD93。CD93 是动脉粥样硬化斑块成像的潜在靶点。