CXCR7 suppression modulates macrophage phenotype and function to ameliorate post-myocardial infarction injury.

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.

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