MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis

Matrix metalloproteinases are involved in vascular remodeling. Little is known about their immune regulatory role in atherosclerosis. Here we show that mice deficient for MT4-MMP have increased adherence of macrophages to inflamed peritonea, and larger lipid deposits and macrophage burden in atheros...

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Autores: Clemente, Cristina, Rius, Cristina, Alonso-Herranz, Laura, Martin-Alonso, Mara, Pollan, Angela, Camafeita, Emilio, Martinez, Fernando, Mota, Ruben A., Nunez, Vanessa, Rodriguez, Cristina, Seiki, Motoharu, Martinez-Gonzalez, Jose, Andres, Vicente, Ricote, Mercedes, Arroyo, Alicia G
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6684
Acceso en línea:http://hdl.handle.net/20.500.12105/6684
Access Level:acceso abierto
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spelling MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosisClemente, CristinaRius, CristinaAlonso-Herranz, LauraMartin-Alonso, MaraPollan, AngelaCamafeita, EmilioMartinez, FernandoMota, Ruben A.Nunez, VanessaRodriguez, CristinaSeiki, MotoharuMartinez-Gonzalez, JoseAndres, VicenteRicote, MercedesArroyo, Alicia GMatrix metalloproteinases are involved in vascular remodeling. Little is known about their immune regulatory role in atherosclerosis. Here we show that mice deficient for MT4-MMP have increased adherence of macrophages to inflamed peritonea, and larger lipid deposits and macrophage burden in atherosclerotic plaques. We also demonstrate that MT4-MMP deficiency results in higher numbers of patrolling monocytes crawling and adhered to inflamed endothelia, and the accumulation of Mafb+ apoptosis inhibitor of macrophage (AIM)+ macrophages at incipient atherosclerotic lesions in mice. Functionally, MT4-MMP-null Mafb+ AIM+ peritoneal macrophages express higher AIM and scavenger receptor CD36, are more resistant to apoptosis, and bind acLDL avidly, all of which contribute to atherosclerosis. CCR5 inhibition alleviates these effects by hindering the enhanced recruitment of MT4-MMP-null patrolling monocytes to early atherosclerotic lesions, thus blocking Mafb+ AIM+ macrophage accumulation and atherosclerosis acceleration. Our results suggest that MT4-MMP targeting may constitute a novel strategy to boost patrolling monocyte activity in early inflammation.Nature Publishing GroupMinisterio de Economía, Industria y Competitividad (España)Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Fundación La Marató TV3Fundación ProCNIC20182018-11-2220182018-01-0120182018-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/pdfapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheetapplication/octet-streamapplication/octet-streamapplication/octet-streamapplication/octet-streamhttp://hdl.handle.net/20.500.12105/6684reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES RD12 0042ES SAF2014-52050R Not availableES SAF2017-83229R Not availableES SEV-2015-0505 Not availableES SAF2015-64287R Not availableES SAF2015-71878-REDT Not availableES RD12 0042ES SAF2015-64767-R Not availableES SAF2016-79490-R Not availableES RD12 0042ES FPDI-2013-17423 Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/66842026-06-12T12:43:37Z
dc.title.none.fl_str_mv MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis
title MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis
spellingShingle MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis
Clemente, Cristina
title_short MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis
title_full MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis
title_fullStr MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis
title_full_unstemmed MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis
title_sort MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis
dc.creator.none.fl_str_mv Clemente, Cristina
Rius, Cristina
Alonso-Herranz, Laura
Martin-Alonso, Mara
Pollan, Angela
Camafeita, Emilio
Martinez, Fernando
Mota, Ruben A.
Nunez, Vanessa
Rodriguez, Cristina
Seiki, Motoharu
Martinez-Gonzalez, Jose
Andres, Vicente
Ricote, Mercedes
Arroyo, Alicia G
author Clemente, Cristina
author_facet Clemente, Cristina
Rius, Cristina
Alonso-Herranz, Laura
Martin-Alonso, Mara
Pollan, Angela
Camafeita, Emilio
Martinez, Fernando
Mota, Ruben A.
Nunez, Vanessa
Rodriguez, Cristina
Seiki, Motoharu
Martinez-Gonzalez, Jose
Andres, Vicente
Ricote, Mercedes
Arroyo, Alicia G
author_role author
author2 Rius, Cristina
Alonso-Herranz, Laura
Martin-Alonso, Mara
Pollan, Angela
Camafeita, Emilio
Martinez, Fernando
Mota, Ruben A.
Nunez, Vanessa
Rodriguez, Cristina
Seiki, Motoharu
Martinez-Gonzalez, Jose
Andres, Vicente
Ricote, Mercedes
Arroyo, Alicia G
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía, Industria y Competitividad (España)
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Fundación La Marató TV3
Fundación ProCNIC
description Matrix metalloproteinases are involved in vascular remodeling. Little is known about their immune regulatory role in atherosclerosis. Here we show that mice deficient for MT4-MMP have increased adherence of macrophages to inflamed peritonea, and larger lipid deposits and macrophage burden in atherosclerotic plaques. We also demonstrate that MT4-MMP deficiency results in higher numbers of patrolling monocytes crawling and adhered to inflamed endothelia, and the accumulation of Mafb+ apoptosis inhibitor of macrophage (AIM)+ macrophages at incipient atherosclerotic lesions in mice. Functionally, MT4-MMP-null Mafb+ AIM+ peritoneal macrophages express higher AIM and scavenger receptor CD36, are more resistant to apoptosis, and bind acLDL avidly, all of which contribute to atherosclerosis. CCR5 inhibition alleviates these effects by hindering the enhanced recruitment of MT4-MMP-null patrolling monocytes to early atherosclerotic lesions, thus blocking Mafb+ AIM+ macrophage accumulation and atherosclerosis acceleration. Our results suggest that MT4-MMP targeting may constitute a novel strategy to boost patrolling monocyte activity in early inflammation.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-11-22
2018
2018-01-01
2018
2018-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/6684
url http://hdl.handle.net/20.500.12105/6684
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES RD12 0042
ES SAF2014-52050R Not available
ES SAF2017-83229R Not available
ES SEV-2015-0505 Not available
ES SAF2015-64287R Not available
ES SAF2015-71878-REDT Not available
ES RD12 0042
ES SAF2015-64767-R Not available
ES SAF2016-79490-R Not available
ES RD12 0042
ES FPDI-2013-17423 Not available
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
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application/pdf
application/pdf
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
application/octet-stream
application/octet-stream
application/octet-stream
application/octet-stream
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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