| First Author | Kubota A | Year | 2019 |
| Journal | J Mol Cell Cardiol | Volume | 131 |
| Pages | 41-52 | PubMed ID | 31009606 |
| Mgi Jnum | J:275924 | Mgi Id | MGI:6305019 |
| Doi | 10.1016/j.yjmcc.2019.04.007 | Citation | Kubota A, et al. (2019) Matrix metalloproteinase-12 produced by Ly6C(low) macrophages prolongs the survival after myocardial infarction by preventing neutrophil influx. J Mol Cell Cardiol 131:41-52 |
| abstractText | BACKGROUND: Various immune cells are involved in different phases of cardiac repair after myocardial infarction (MI). Especially, Ly6C(low) M2-like macrophages (Ly6C(lo) macrophages) are vital for cardiac repair after MI. However, the molecular mechanisms how Ly6C(lo) macrophages promote wound healing after MI are still largely unknown. METHODS AND RESULTS: Transcriptome analysis of Ly6C(lo) macrophages and Ly6C(high) M1-like macrophages (Ly6C(hi) macrophages) harvested from the infarcted heart revealed that Ly6C(lo) macrophages highly expressed matrix metalloproteinase (MMP)-12 mRNA compared to Ly6C(hi) macrophages. MMP-12 expression was enhanced in the infarcted heart and preferentially observed in Ly6C(lo) macrophages. Importantly, the survival rate and cardiac function after MI were significantly impaired in MMP-12-deficient (mmp12(-/-)) mice compared with those in wild-type mice. In addition, the extent of myocardial fibrosis and the number of myofibroblasts in the infarct area were decreased in mmp12(-/-) mice. MMP-9 expression and neutrophils, which are the major cellular source of MMP-9, in the infarcted heart were increased in mmp12(-/-) mice. Moreover, mRNA expression of neutrophil-attracting chemokines including CXCL1, CXCL2, and CXCL5 was significantly higher in mmp12(-/-) mice. Consistently, treatment with anti-CXCR2 antibody significantly decreased neutrophil numbers and MMP-9 expression in the infarcted heart in mmp12(-/-) mice. Finally, the administration of recombinant MMP-12 into the infarcted heart decreased neutrophil numbers in the infarcted heart and promoted wound healing in both wild-type mice and mmp12(-/-) mice. CONCLUSION: MMP-12 produced by Ly6C(lo) macrophages improves the survival after MI possibly through the promotion of wound healing by reducing neutrophil infiltration. |
