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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/194621
Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/ TGF$\beta 1$ after myocardial infarction
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Macrophages (M $\varphi s$ ) 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 M $\varphi$ s increased the expression of Mmp14 (MT1-MMP) 7 days post-MI. We selectively inactivated the $M m p 14$ gene in $\mathrm{M} \varphi$ s using a genetic strategy (Mmp14ff: 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 TGF $\beta 1$ in M $\varphi$ s, 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 $\mathrm{M} \varphi \mathrm{s}$ 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 M $\varphi$ MT1-MMP as a key regulator of this process.
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ALONSO-HERRANZ, Laura, SAHÚN-ESPAÑOL, Álvaro, PAREDES, Ana, GONZALO, Pilar, GKONTRA, Polyxeni, NÚÑEZ, Vanessa, CLEMENTE, Cristina, CEDENILLA, Marta, VILLALBA-ORERO, María, INSERTE, Javier, GARCÍA-DORADO, David, GARCÍA ARROYO, Alicia, RICOTE, Mercedes. Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/ TGF$\beta 1$ after myocardial infarction. _eLife_. 2020. [consulta: 24 de gener de 2026]. ISSN: 2050-084X. [Disponible a: https://hdl.handle.net/2445/194621]