2026-06-27T22:45:37Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/960962024-02-18T01:20:17Zcom_20.500.14352_14col_20.500.14352_15

Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/TGFβ1 after myocardial infarction Alonso-Herranz, Laura Sahún-Español, Álvaro Paredes, Ana Gonzalo, Pilar Gkontra, Polyxeni Núñez, Vanessa Clemente, Cristina Cedenilla, Marta Inserte, Javier García-Dorado, David G Arroyo, Alicia Ricote, Mercedes Villalba Orero, María Macrophages (Mφs) 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 Mφs increased the expression of Mmp14 (MT1-MMP) 7 days post-MI. We selectively inactivated the Mmp14 gene in Mφs using a genetic strategy (Mmp14f/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 TGFβ1 in Mφs, 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 Mφs 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 Mφ MT1-MMP as a key regulator of this process. 2024-01-29T13:25:22Z 2024-01-29T13:25:22Z 2024-01-29T13:25:22Z 2020-10-16 journal article https://hdl.handle.net/20.500.14352/96096 2050-084X 10.7554/elife.57920 eng B http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International eLife Sciences Publications