CXCR7 suppression modulates macrophage phenotype and function to ameliorate post-myocardial infarction injury
- 13 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Inflammation Research
- Vol. 69 (5), 523-532
- https://doi.org/10.1007/s00011-020-01335-z
Abstract
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.Keywords
Funding Information
- Xinjiang Uygur Autonomous Region Natural Science Foundation (2018D01C307)
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