2026-04-24T11:48:09Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/131822024-10-31T11:54:58Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Alonso-Herranz, Laura
author
Sahun-Español, Alvaro
author
Paredes, Ana
author
Gonzalo, Pilar
author
Gkontra, Polyxeni
author
Nunez, Vanessa
author
Clemente, Cristina
author
Cedenilla, Marta
author
Villalba-Orero, Maria
author
Inserte, Javier
author
Garcia-Dorado, David
author
Arroyo, Alicia G
author
Ricote, Mercedes
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Comunidad de Madrid (España)
funder
Fundación La Marató TV3
funder
Fundación La Caixa
funder
Fundación ProCNIC
2021-06-23T08:30:25Z
2021-06-23T08:30:25Z
2020-10
Elife. 2020; 9:e57920
http://hdl.handle.net/20.500.12105/13182
33063665
10.7554/eLife.57920
2050-084X
eLife
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.
eng
Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/TGFβ1 after myocardial infarction.
journal article
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