机构：[1]Center for Neuroimmunology and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China[2]Tongji University School of Medicine, Shanghai, China[3]Division of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[4]Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, China[5]Department of Pharmacology and Experimental Neurosciences, Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, USA
Endothelial injuries, including cell pyroptosis, are ongoing inflammatory processes with key roles in atherosclerosis development. Our previous report showed that the chemokine CXCL12 and its receptor CXCR7 are associated with the proliferation and angiogenesis of endothelial cells. Nevertheless, the mechanism underlying these effects on atherosclerotic lesions, especially on endothelial dysfunction, remains unknown. Here, we demonstrated that CXCR7 was upregulated in human carotid atherosclerotic plaques, apolipoprotein E knockout (ApoE(-/-)) mice fed with a high-fat diet (HFD), and oxidized lipopolysaccharide-treated (ox-LDL) human umbilical vein endothelial cells (HUVECs). Further, the activation of CXCR7 reversed ox-LDL-induced HUVEC dysfunction, such as migration, tube formation, and cell pyroptosis; all of these protective effects were alleviated by inhibition of CXCR7. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes were also elevated in human carotid atherosclerotic plaques, ApoE(-/-)mice fed with HFD, and ox-LDL-injured HUVECs by regulation of caspase-1 and interleukin (IL)-1 beta expression. The activation of CXCR7 by TC14012 led to a decrease in atherosclerotic lesions in ApoE(-/-)mice fed with HFD. TC14012 also inhibited the expression of the NLRP3 inflammasome signaling pathwayin vivo. In conclusion, our study suggests that CXCR7 plays an important role in regulating NLRP3 inflammasome-modulated pyroptosis in HUVECs, providing a potential novel therapy for atherosclerosis.
基金：
National Natural Science Foundation
of China: 91949204; National Natural
Science Foundation of China, Grant/Award
Number: 81830037; National Institute
of Neurological Disorders and Stroke,
Grant/Award Number: 1R01NS097195;
National Basic Research Program of China
(973 Program), Grant/Award Number:
2014CB965001
第一作者机构：[1]Center for Neuroimmunology and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China[2]Tongji University School of Medicine, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[1]Center for Neuroimmunology and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China[3]Division of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[4]Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, China[5]Department of Pharmacology and Experimental Neurosciences, Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE, USA[*1]Center for Neuroimmunology and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China.[*2]Division of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai 200336, China.
推荐引用方式(GB/T 7714)：
Qiu Lisha,Zhang Min,Zhang Sheng,et al.Activation of CXCR7 promotes endothelial repair and reduces the carotid atherosclerotic lesions through inhibition of pyroptosis signaling pathways[J].AGING CELL.2020,19(9):doi:10.1111/acel.13205.
APA：
Qiu, Lisha,Zhang, Min,Zhang, Sheng,Tang, Yalin,Zhang, Yanyan...&Zheng, Jialin C..(2020).Activation of CXCR7 promotes endothelial repair and reduces the carotid atherosclerotic lesions through inhibition of pyroptosis signaling pathways.AGING CELL,19,(9)
MLA：
Qiu, Lisha,et al."Activation of CXCR7 promotes endothelial repair and reduces the carotid atherosclerotic lesions through inhibition of pyroptosis signaling pathways".AGING CELL 19..9(2020)
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