MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport

Objective: To determine whether miR-125b regulates cholesterol efflux in vivo and in vitro through the regulation of scavenger receptor type B1 (SR-B1). Approach and results: We demonstrated that miR-125b is up-regulated in the human aortas of patients with CAD and is located in macrophages and vasc...

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Autores: Hueso, Miguel|||0000-0002-1824-9141, Griñán, Raquel|||0000-0002-9457-3365, Mallen, Adrián, Navarro, Estanislao, Purqueras, Elvira, Gomà-Gállego, Montserrat, Sbraga, Fabrizio, Blasco-Lucas, Arnau|||0000-0002-2796-7428, Revilla, Giovanna|||0000-0003-2971-5651, Santos, David|||0000-0003-1157-4969, Canyelles, Marina|||0000-0002-0278-5337, Julve i Gil, Josep|||0000-0002-6531-2246, Escolà-Gil, Joan Carles|||0000-0001-9021-2485, Rotllan, Noemi|||0000-0002-0587-8045
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:282279
Acceso en línea:https://ddd.uab.cat/record/282279
https://dx.doi.org/urn:doi:10.1016/j.biopha.2021.112596
Access Level:acceso abierto
Palabra clave:Cholesterol efflux
Reverse cholesterol transport
Scavenger receptor class B type 1 (SRB1)
MicroRNA
MiR-125b
Macrophage
Vascular smooth muscle cell
Coronary artery disease
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spelling MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transportHueso, Miguel|||0000-0002-1824-9141Griñán, Raquel|||0000-0002-9457-3365Mallen, AdriánNavarro, EstanislaoPurqueras, ElviraGomà-Gállego, MontserratSbraga, FabrizioBlasco-Lucas, Arnau|||0000-0002-2796-7428Revilla, Giovanna|||0000-0003-2971-5651Santos, David|||0000-0003-1157-4969Canyelles, Marina|||0000-0002-0278-5337Julve i Gil, Josep|||0000-0002-6531-2246Escolà-Gil, Joan Carles|||0000-0001-9021-2485Rotllan, Noemi|||0000-0002-0587-8045Cholesterol effluxReverse cholesterol transportScavenger receptor class B type 1 (SRB1)MicroRNAMiR-125bMacrophageVascular smooth muscle cellCoronary artery diseaseObjective: To determine whether miR-125b regulates cholesterol efflux in vivo and in vitro through the regulation of scavenger receptor type B1 (SR-B1). Approach and results: We demonstrated that miR-125b is up-regulated in the human aortas of patients with CAD and is located in macrophages and vascular smooth muscle cells (VSMCs). We identified SCARB1 as a direct target of miR-125b by repressing the activity of the SCARB1 3'-untranslated region reporter construct. Moreover, the overexpression of miR-125b in both human and mouse macrophages as well as VSMCs was found to downregulated the expression of the SCARB1 and the SR-B1 protein levels, thereby impairing α-HDL-mediated macrophage cholesterol efflux in vitro. The in vivo reverse cholesterol transport (RCT) rate from non-cholesterol-loaded macrophages transfected with miR-125b to feces was also found to be decreased when compared with that of control mimic-transfected macrophages. Conclusions: Together, these results provide evidence that miR-125b downregulates SCARB1 and SR-B1 in both human and mouse macrophages as well as VSMCs, thereby impairing macrophage cholesterol efflux in vitro and the whole macrophage-specific RCT pathway in vivo.Universitat Autònoma de Barcelona 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/282279https://dx.doi.org/urn:doi:10.1016/j.biopha.2021.112596reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 PID2019-104367RB-100Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RYC-201722879Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/01108Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CM20/00033Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/00232Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CPII18/00004open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2822792026-06-06T12:50:31Z
dc.title.none.fl_str_mv MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport
title MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport
spellingShingle MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport
Hueso, Miguel|||0000-0002-1824-9141
Cholesterol efflux
Reverse cholesterol transport
Scavenger receptor class B type 1 (SRB1)
MicroRNA
MiR-125b
Macrophage
Vascular smooth muscle cell
Coronary artery disease
title_short MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport
title_full MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport
title_fullStr MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport
title_full_unstemmed MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport
title_sort MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport
dc.creator.none.fl_str_mv Hueso, Miguel|||0000-0002-1824-9141
Griñán, Raquel|||0000-0002-9457-3365
Mallen, Adrián
Navarro, Estanislao
Purqueras, Elvira
Gomà-Gállego, Montserrat
Sbraga, Fabrizio
Blasco-Lucas, Arnau|||0000-0002-2796-7428
Revilla, Giovanna|||0000-0003-2971-5651
Santos, David|||0000-0003-1157-4969
Canyelles, Marina|||0000-0002-0278-5337
Julve i Gil, Josep|||0000-0002-6531-2246
Escolà-Gil, Joan Carles|||0000-0001-9021-2485
Rotllan, Noemi|||0000-0002-0587-8045
author Hueso, Miguel|||0000-0002-1824-9141
author_facet Hueso, Miguel|||0000-0002-1824-9141
Griñán, Raquel|||0000-0002-9457-3365
Mallen, Adrián
Navarro, Estanislao
Purqueras, Elvira
Gomà-Gállego, Montserrat
Sbraga, Fabrizio
Blasco-Lucas, Arnau|||0000-0002-2796-7428
Revilla, Giovanna|||0000-0003-2971-5651
Santos, David|||0000-0003-1157-4969
Canyelles, Marina|||0000-0002-0278-5337
Julve i Gil, Josep|||0000-0002-6531-2246
Escolà-Gil, Joan Carles|||0000-0001-9021-2485
Rotllan, Noemi|||0000-0002-0587-8045
author_role author
author2 Griñán, Raquel|||0000-0002-9457-3365
Mallen, Adrián
Navarro, Estanislao
Purqueras, Elvira
Gomà-Gállego, Montserrat
Sbraga, Fabrizio
Blasco-Lucas, Arnau|||0000-0002-2796-7428
Revilla, Giovanna|||0000-0003-2971-5651
Santos, David|||0000-0003-1157-4969
Canyelles, Marina|||0000-0002-0278-5337
Julve i Gil, Josep|||0000-0002-6531-2246
Escolà-Gil, Joan Carles|||0000-0001-9021-2485
Rotllan, Noemi|||0000-0002-0587-8045
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Cholesterol efflux
Reverse cholesterol transport
Scavenger receptor class B type 1 (SRB1)
MicroRNA
MiR-125b
Macrophage
Vascular smooth muscle cell
Coronary artery disease
topic Cholesterol efflux
Reverse cholesterol transport
Scavenger receptor class B type 1 (SRB1)
MicroRNA
MiR-125b
Macrophage
Vascular smooth muscle cell
Coronary artery disease
description Objective: To determine whether miR-125b regulates cholesterol efflux in vivo and in vitro through the regulation of scavenger receptor type B1 (SR-B1). Approach and results: We demonstrated that miR-125b is up-regulated in the human aortas of patients with CAD and is located in macrophages and vascular smooth muscle cells (VSMCs). We identified SCARB1 as a direct target of miR-125b by repressing the activity of the SCARB1 3'-untranslated region reporter construct. Moreover, the overexpression of miR-125b in both human and mouse macrophages as well as VSMCs was found to downregulated the expression of the SCARB1 and the SR-B1 protein levels, thereby impairing α-HDL-mediated macrophage cholesterol efflux in vitro. The in vivo reverse cholesterol transport (RCT) rate from non-cholesterol-loaded macrophages transfected with miR-125b to feces was also found to be decreased when compared with that of control mimic-transfected macrophages. Conclusions: Together, these results provide evidence that miR-125b downregulates SCARB1 and SR-B1 in both human and mouse macrophages as well as VSMCs, thereby impairing macrophage cholesterol efflux in vitro and the whole macrophage-specific RCT pathway in vivo.
publishDate 2022
dc.date.none.fl_str_mv 2
2022-01-01
2022
2022-01-01
dc.type.none.fl_str_mv 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 https://ddd.uab.cat/record/282279
https://dx.doi.org/urn:doi:10.1016/j.biopha.2021.112596
url https://ddd.uab.cat/record/282279
https://dx.doi.org/urn:doi:10.1016/j.biopha.2021.112596
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 PID2019-104367RB-100
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RYC-201722879
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/01108
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CM20/00033
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/00232
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CPII18/00004
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://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
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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