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Title: Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/ TGF$\beta 1$ after myocardial infarction
Author: 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
Keywords: Infart de miocardi
Codi genètic
Cultiu cel·lular
Malalties cardiovasculars
Myocardial infarction
Genetic code
Cell culture
Cardiovascular diseases
Issue Date: 16-Oct-2020
Publisher: eLife Sciences
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: eLife, 2020
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ISSN: 2050-084X
Appears in Collections:Articles publicats en revistes (Matemàtiques i Informàtica)

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