CXCR7 抑制调节巨噬细胞表型和功能，改善心肌梗死后损伤。
CXCR7 suppression modulates macrophage phenotype and function to ameliorate post-myocardial infarction injury.
机构信息
Department of Hypertension, Heart Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China.
Department of Cardiology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China.
出版信息
Inflamm Res. 2020 May;69(5):523-532. doi: 10.1007/s00011-020-01335-z. Epub 2020 Mar 13.
OBJECTIVE
Myocardial infarction (MI) is one of the primary causes leading to heart failure in coronary artery disease. However, the mechanisms of macrophage that dominate pathogenesis of MI remain unclear.
METHODS
Mice were induced with MI and pretreated with adenovirus containing indicated shRNA. Post-MI injuries were evaluated by echocardiography. BMDMs and post-MI LV macrophages were used to assess the significance of CXCR7. Macrophages' migration was examined by chemotaxis assay, Cytokine production, phosphorylation of ERK1/2, p38 MAPK and JNK were measured by ELISA.
RESULTS
CXCR7 in macrophages was up-regulated during M1 polarization and following MI in the murine model, with positive correlation with M1 markers but not M2 markers. Besides, CXCR7 down-regulation abolished macrophage M1 polarization. In addition, CXCR7 but not CXCR3 or CXCR4 controlled SDF-1 and I-TAC-mediated chemotaxis and inflammation in M1-like macrophages post-MI, signaling through activating ERK1/2, whereas p38 MAPK and JNK were not involved. Moreover, silencing CXCR7 ameliorated cardiac dysfunction by attenuating infarct area, LVEF and LVFS post-MI along with reduction of CXCR7 expression and ERK1/2 phosphorylation.
CONCLUSIONS
Our data demonstrate that CXCR7 suppression inhibits macrophages M1 polarization, chemotaxis and inflammation to ameliorate post-MI injury, providing novel insights and promising therapy approaches in post-MI treatment.
目的
心肌梗死（MI）是导致冠心病心力衰竭的主要原因之一。然而，巨噬细胞在 MI 发病机制中起主导作用的机制尚不清楚。
方法
通过腺病毒转染含目的 shRNA 预处理 MI 诱导的小鼠。通过超声心动图评估心肌梗死后损伤。使用 BMDM 和 MI 后 LV 巨噬细胞评估 CXCR7 的意义。通过趋化实验检测巨噬细胞的迁移，通过 ELISA 检测细胞因子的产生、ERK1/2、p38 MAPK 和 JNK 的磷酸化。
结果
在 MI 后小鼠模型中，巨噬细胞中的 CXCR7 在 M1 极化过程中上调，与 M1 标志物呈正相关，但与 M2 标志物无关。此外，下调 CXCR7 可消除巨噬细胞 M1 极化。此外，CXCR7 而非 CXCR3 或 CXCR4 控制 MI 后 M1 样巨噬细胞中 SDF-1 和 I-TAC 介导的趋化作用和炎症，通过激活 ERK1/2 起作用，而 p38 MAPK 和 JNK 不参与。此外，沉默 CXCR7 通过减轻 CXCR7 表达和 ERK1/2 磷酸化来改善 MI 后心脏功能障碍，减少梗死面积、LVEF 和 LVFS。
结论
我们的数据表明，CXCR7 抑制抑制巨噬细胞 M1 极化、趋化和炎症，改善 MI 后损伤，为 MI 后治疗提供新的见解和有前景的治疗方法。
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