Zhan Hu, Min Dai, Yuan Chang, Xiumeng Hua, Ningning Zhang, Xiao Chen, Yixuan Sheng, Zhenyu Xu, Hang Zhang, Yu Zhang, Hao Cui, Hao Jia, Xiu-Jie Wang, Jiangping Song
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Fibroblasts from the RA and RGA highly expressed GDF10 and CREB5, respectively; both GDF10 and CREB5 are associated with extracellular matrix deposition. Cell–cell communication analysis revealed high levels of macrophage migration inhibitory factor signaling in the RA. Administration of macrophage migration inhibitory factor inhibitor to mice with partial carotid artery ligation blocked neointimal hyperplasia induced by disturbed flow. Modulation of identified targets may have protective effects on arterial grafts. 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引用次数: 0
摘要
冠状动脉旁路移植术中常用的动脉移植物包括胸内动脉(ITA)、桡动脉(RA)和右胃网膜动脉(RGA)移植物;其中,ITA 的临床效果最好。在此,通过分析不同动脉移植物的单细胞转录组,我们以 ITA 为参考,提出了 RA 和 RGA 的优化策略。与 ITA 相比,RA 有更多与脂质处理相关的 CD36+ 内皮细胞。RGA的血管平滑肌细胞更容易受到痉挛的影响,其次是RA的血管平滑肌细胞;与ITA的比较表明,钾通道开放剂可能会对抗血管痉挛。RA和RGA的成纤维细胞分别高表达GDF10和CREB5;GDF10和CREB5都与细胞外基质沉积有关。细胞-细胞通讯分析显示,RA的巨噬细胞迁移抑制因子信号水平较高。给部分颈动脉结扎的小鼠注射巨噬细胞迁移抑制因子抑制剂可阻断血流紊乱诱导的新内膜增生。调节已确定的靶点可能会对动脉移植物产生保护作用。基于胸内动脉、桡动脉和右胃底动脉移植物的单细胞转录组学比较,Hu、Dai、Chang 等人发现了可防止细胞外基质沉积和纤维化并改善冠状动脉旁路移植术效果的因素。
Strategies for arterial graft optimization at the single-cell level
Common arterial grafts used in coronary artery bypass grafting include internal thoracic artery (ITA), radial artery (RA) and right gastroepiploic artery (RGA) grafts; of these, the ITA has the best clinical outcome. Here, by analyzing the single-cell transcriptome of different arterial grafts, we suggest optimization strategies for the RA and RGA based on the ITA as a reference. Compared with the ITA, the RA had more lipid-handling-related CD36+ endothelial cells. Vascular smooth muscle cells from the RGA were more susceptible to spasm, followed by those from the RA; comparison with the ITA suggested that potassium channel openers may counteract vasospasm. Fibroblasts from the RA and RGA highly expressed GDF10 and CREB5, respectively; both GDF10 and CREB5 are associated with extracellular matrix deposition. Cell–cell communication analysis revealed high levels of macrophage migration inhibitory factor signaling in the RA. Administration of macrophage migration inhibitory factor inhibitor to mice with partial carotid artery ligation blocked neointimal hyperplasia induced by disturbed flow. Modulation of identified targets may have protective effects on arterial grafts. Based on comparative single-cell transcriptomics of arterial grafts deriving from internal thoracic, radial and right gastroepiploic arteries, Hu, Dai, Chang, et al. identify factors that might prevent extracellular matrix deposition and fibrosis and improve the outcomes of coronary artery bypass grafting.