CCL7 contributes to angiotensin II-induced abdominal aortic aneurysm by promoting macrophage infiltration and pro-inflammatory phenotype.
CCL7 contributes to angiotensin II-induced abdominal aortic aneurysm by promoting macrophage infiltration and pro-inflammatory phenotype.
复制标题
CCL7通过促进巨噬细胞浸润和促炎表型而促成血管紧张素II诱导的腹主动脉瘤。
DOI：
10.1111/jcmm.16757
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发表时间：
2021-08
影响因子：
5.3
通讯作者：
Xie X
中科院分区：
文献类型：
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作者：
Xie C;Ye F;Zhang N;Huang Y;Pan Y;Xie X
趋化因子C - C基序配体7 （CCL7）是CC趋化因子亚家族的一员，在许多炎症性疾病中起着关键作用。炎症过度激活是腹主动脉瘤（AAA）的一个重要特征。因此，在本研究中，我们旨在确定CCL7对AAA形成的影响。血管紧张素II （Ang II）诱导的AAA小鼠主动脉组织和巨噬细胞浸润中的CCL7丰度均增加。在体外，CCL7促进巨噬细胞向M1表型极化。阻断CCR1 （CCL7的一种受体）可以逆转这种效应。CCL7上调巨噬细胞中JAK2/STAT1蛋白水平，通过抑制JAK2/STAT1通路抑制CCL7诱导的M1活化。为了验证CCL7在体内对AAA的影响，在Ang II输注前24小时腹腔注射CCL7 -中和抗体（CCL7 - nAb）或载体，随后每三天注射一次，持续4周。CCL7 - nAb可显著减弱Ang II诱导的腔内和外扩张以及病理重构。免疫染色显示CCL7‐nAb可显著降低动脉瘤巨噬细胞浸润。综上所述，CCL7通过CCR1/JAK2/STAT1信号通路促进巨噬细胞M1表型，从而促进了Ang II诱导的AAA。
Chemokine C‐C motif ligand 7 (CCL7), a member of CC chemokine subfamily, plays pivotal roles in numerous inflammatory diseases. Hyper‐activation of inflammation is an important characteristic of abdominal aortic aneurysm (AAA). Therefore, in the present study, we aimed to determine the effect of CCL7 on AAA formation. CCL7 abundance in aortic tissue and macrophage infiltration were both increased in angiotensin II (Ang II)‐induced AAA mice. Ex vivo, CCL7 promoted macrophage polarization towards M1 phenotype. This effect was reversed by the blockage of CCR1, a receptor of CCL7. CCL7 up‐regulated JAK2/STAT1 protein level in macrophage, and CCL7‐induced M1 activation was suppressed by JAK2/STAT1 pathway inhibition. To verify the effect of CCL7 on AAA in vivo, either CCL7‐neutralizing antibody (CCL7‐nAb) or vehicles were intraperitoneally injected 24 hours prior to Ang II infusion and subsequently every three days for 4 weeks. CCL7‐nAb administration significantly attenuated Ang II‐induced luminal and external dilation as well as pathological remodelling. Immunostaining showed that CCL7‐nAb administration significantly decreased aneurysmal macrophage infiltration. In conclusion, CCL7 contributed to Ang II‐induced AAA by promoting M1 phenotype of macrophage through CCR1/JAK2/STAT1 signalling pathway.
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DOI：
10.3791/1291
发表时间：
2009-05-15
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Daugherty, Alan;Rateri, Debra;Balakrishnan, Anju
通讯作者：
Balakrishnan, Anju
影响因子：
7.3
作者：
Ford, Jill;Hughson, Angela;Fowell, Deborah J.
通讯作者：
Fowell, Deborah J.
影响因子：
20.1
作者：
Huang J;Zhang Z;Guo J;Ni A;Deb A;Zhang L;Mirotsou M;Pratt RE;Dzau VJ
通讯作者：
Dzau VJ
DOI：
10.1161/atvbaha.120.315398
发表时间：
2021-01-01
影响因子：
8.7
作者：
Chiang, Ming-Tsai;Chen, I-Ming;Chau, Lee-Young
通讯作者：
Chau, Lee-Young
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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