RT Journal Article
T1 Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/TGFβ1 after myocardial infarction
A1 Alonso-Herranz, Laura
A1 Sahún-Español, Álvaro
A1 Paredes, Ana
A1 Gonzalo, Pilar
A1 Gkontra, Polyxeni
A1 Núñez, Vanessa
A1 Clemente, Cristina
A1 Cedenilla, Marta
A1 Inserte, Javier
A1 García-Dorado, David
A1 G Arroyo, Alicia
A1 Ricote, Mercedes
A1 Villalba Orero, María
AB 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.
PB eLife Sciences Publications
SN 2050-084X
YR 2020
FD 2020-10-16
LK https://hdl.handle.net/20.500.14352/96096
UL https://hdl.handle.net/20.500.14352/96096
LA eng
NO Author contributions Laura Alonso-Herranz, Conceptualization, Data curation, Software, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing-original draft; Álvaro Sahón-Español, Pilar Gonzalo, Data curation, Software, Formal analysis, Investigation, Visualization, Methodology, Writing- review and editing; Ana Paredes, Marta Cedenilla, Javier Inserte, Formal analysis, Investigation, Methodology; Polyxeni Gkontra, Data curation, Software, Formal analysis, Methodology, Writing-review and editing; Vanessa Nuñez, Cristina Clemente, Methodology; María Villalba-Orero, Software, Formal analysis, Validation, Visualization, Methodology; David García-Dorado, Conceptualization, Resources, Investigation, Writing-review and editing; Alicia G Arroyo, Conceptualization, Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Writing-original draft, Project administration, Writing- review and editing; Mercedes Ricote, Conceptualization, Resources, Supervision, Funding acquisition, Validation, Investigation,Writing-original draft, Project administration, Writing-review and editing.
NO Ministerio de Ciencia, Innovación y Universidades (SAF2017-90604-REDT-NurCaMeIn; RTI2018-095928-BI00; SAF2017-83229-R; BES-2016-076632
NO Comunidad de Madrid (MOIR-B2017/BMD-3684)
NO La Marato TV3 Foundation
NO Fundacion LaCaixa
NO La Residencia de Estudiantes
NO FORD-Spain and Apadrina La Ciencia
DS Docta Complutense
RD 6 abr 2025