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.

中文翻译：

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CXCR7抑制调节巨噬细胞表型和功能，以减轻心肌梗塞后损伤

目的

心肌梗塞（MI）是导致冠心病的心力衰竭的主要原因之一。然而，尚不清楚支配MI发病机制的巨噬细胞的机制。

方法

用MI诱导小鼠并用含有所示shRNA的腺病毒预处理。MI后损伤通过超声心动图评估。使用BMDM和MI后LV巨噬细胞评估CXCR7的重要性。通过趋化分析检测巨噬细胞的迁移，通过ELISA测量细胞因子的产生，ERK1 / 2，p38 MAPK和JNK的磷酸化。

结果

巨噬细胞中的CXCR7在M1极化过程中和鼠模型中的MI后上调，与M1标记呈正相关，但与M2标记无正相关。此外，CXCR7下调取消了巨噬细胞M1极化。此外，MI后M1样巨噬细胞中CXCR7而不是CXCR3或CXCR4控制SDF-1和I-TAC介导的趋化性和炎症，通过激活ERK1 / 2发出信号，而p38 MAPK和JNK不参与。此外，沉默CXCR7可通过减轻梗死面积，MI后的LVEF和LVFS以及减少CXCR7表达和ERK1 / 2磷酸化来改善心脏功能障碍。

结论

我们的数据表明，CXCR7抑制可抑制巨噬细胞M1极化，趋化性和炎症，从而改善MI后损伤，为MI后治疗提供新的见识和有希望的治疗方法。