| First Author | Alonso-Herranz L | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 33063665 | Mgi Jnum | J:311403 |
| Mgi Id | MGI:6717674 | Doi | 10.7554/eLife.57920 |
| Citation | Alonso-Herranz L, et al. (2020) Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/TGFbeta1 after myocardial infarction. Elife 9:e57920 |
| abstractText | Macrophages (Mphis) produce factors that participate in cardiac repair and remodeling after myocardial infarction (MI); however, how these factors crosstalk with other cell types mediating repair is not fully understood. Here we demonstrated that cardiac Mphis increased the expression of Mmp14 (MT1-MMP) 7 days post-MI. We selectively inactivated the Mmp14 gene in Mphis using a genetic strategy (Mmp14(f/f):Lyz2-Cre). This conditional KO (MAC-Mmp14 KO) resulted in attenuated post-MI cardiac dysfunction, reduced fibrosis, and preserved cardiac capillary network. Mechanistically, we showed that MT1-MMP activates latent TGFbeta1 in Mphis, leading to paracrine SMAD2-mediated signaling in endothelial cells (ECs) and endothelial-to-mesenchymal transition (EndMT). Post-MI MAC-Mmp14 KO hearts contained fewer cells undergoing EndMT than their wild-type counterparts, and Mmp14-deficient Mphis showed a reduced ability to induce EndMT in co-cultures with ECs. Our results indicate the contribution of EndMT to cardiac fibrosis and adverse remodeling post-MI and identify Mphi MT1-MMP as a key regulator of this process. |
