@misc{10481/57311,
year = {2019},
month = {6},
url = {http://hdl.handle.net/10481/57311},
abstract = {Upon inflammation, monocyte-derived macrophages (MF) infiltrate blood vessels to
regulate several processes involved in vascular pathophysiology. However, little is known about
the mediators involved. Macrophage polarization is crucial for a fast and e cient initial response
(GM-MF) and a good resolution (M-MF) of the inflammatory process. The functional activity of
polarized MF is exerted mainly through their secretome, which can target other cell types, including
endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and MF
that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a
soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated
pathologies. The aim of this work was to identify components of the MF secretome involved in
the shedding of soluble endoglin. We find that the GM-MF secretome contains metalloprotease 12
(MMP-12), a GM-MF specific marker that may account for the anti-angiogenic activity of the GM-MF
secretome. Cell surface endoglin is present in both GM-MF and M-MF, but soluble endoglin is
only detected in GM-MF culture supernatants. Moreover, MMP-12 is responsible for the shedding
of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both MF and
endothelial cells. These data demonstrate a direct correlation between GM-MF polarization, MMP-12,
and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent
a novel mediator involved in vascular homeostasis.},
organization = {Ministerio de Ciencia, Innovación y Universidades of Spain
(SAF2013-43421-R to C.B.; SAF2017-83785-R and SAF2014-23801 to A.L.C.)},
organization = {Consejo Superior de Investigaciones
Cientificas (201920E022 to C.B.)},
organization = {Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER;
ISCIII-CB06/07/0038 to C.B.)},
organization = {Czech Republic Specific University Research (SVV-260414 to P.N.)},
organization = {CIBERER is
an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain supported by FEDER funds},
organization = {M.A. was funded
with a fellowship from Ministerio de Ciencia e Innovación (BES-2008-003888)},
organization = {M.V. was supported by a short-term
mobility fellowship from the European Erasmus Programme},
publisher = {MDPI},
keywords = {Monocytes},
keywords = {Macrophages},
keywords = {Endothelial cells},
keywords = {Inflammation},
keywords = {MMP-12},
keywords = {endoglin},
title = {MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells},
doi = {10.3390/ijms20123107},
author = {Aristorena, Mikel and Gallardo-Vara, Eunate and Vicen, Matej and de Las Casas-Engel, Mateo and Ojeda-Fernandez, Luisa and Nieto, Concepción and Blanco, Francisco J. and Valbuena-Diez, Ana C. and Botella, Luisa M. and Nachtigal, Petr and Corbi, Angel L. and Colmenares, María and Bernabeu, Carmelo},
}