Opposing effects on vascular smooth muscle cell proliferation and macrophage-induced inflammation reveal a protective role for the proresolving lipid mediator receptor ChemR23 in intimal hyperplasia

Intimal hyperplasia remains a significant clinical problem in for example coronary artery bypass graft failure. Since omega-3 fatty acids reduce intimal hyperplasia, we hypothesized that the G protein-coupled receptor ChemR23 for the omega-3-derived pro-resolving lipid mediator resolvin E1 drives th...

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Autores: Artiach, Gonzalo, Carracedo, Miguel, Clària i Enrich, Joan, Laguna Fernández, Andrés, Bäck, Magnus
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/130457
Acceso en línea:https://hdl.handle.net/2445/130457
Access Level:acceso abierto
Palabra clave:Inflamació
Múscul llis
Malalties vasculars
Inflammation
Smooth muscle
Vascular diseases
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spelling Opposing effects on vascular smooth muscle cell proliferation and macrophage-induced inflammation reveal a protective role for the proresolving lipid mediator receptor ChemR23 in intimal hyperplasiaArtiach, GonzaloCarracedo, MiguelClària i Enrich, JoanLaguna Fernández, AndrésBäck, MagnusInflamacióMúscul llisMalalties vascularsInflammationSmooth muscleVascular diseasesIntimal hyperplasia remains a significant clinical problem in for example coronary artery bypass graft failure. Since omega-3 fatty acids reduce intimal hyperplasia, we hypothesized that the G protein-coupled receptor ChemR23 for the omega-3-derived pro-resolving lipid mediator resolvin E1 drives those effects. ChemR23+/+ and ChemR23-/- mice were generated with or without introduction of the Caenorhabditis elegans fat-1 transgene, which leads to an endogenous omega-3 fatty acid synthesis and thus increasing the substrate for resolvin E1 formation. ChemR23 deletion significantly increased intimal hyperplasia 28 days after ligation of the left common carotid artery. Mice expressing the fat-1 transgene showed reduced intimal hyperplasia independently of ChemR23 expression. ChemR23-/- Vascular smooth muscle cells (VSMCs) exhibited a significantly lower proliferation compared with VSMCs derived from ChemR23+/+ mice. In contrast, ChemR23-/- peritoneal macrophages had significantly higher mRNA levels of pro-inflammatory cytokines compared with ChemR23+/+ macrophages. Finally, conditioned media (CM) transfer from ChemR23-/- macrophages to VSMCs significantly increased VSMC proliferation compared with CM from ChemR23+/+ macrophages. Taken together, these results point to a dual effect of ChemR23 in resolution pharmacology by directly stimulating VSMC proliferation and at the same time suppressing macrophage-induced VSMC proliferation. In conclusion, these differential effects of ChemR23 signaling in VSMC and macrophages open up a novel notion for intimal hyperplasia pathophysiology, where ChemR23-transduced effects on the vascular wall may vary, and even be opposing, depending on the degrees of resolution of inflammation.Frontiers Media2019201920182019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion5 p.application/pdfhttps://hdl.handle.net/2445/130457Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3389/fphar.2018.01327Frontiers in Pharmacology, 2018, vol. 9, p. 1327https://doi.org/10.3389/fphar.2018.01327cc-by (c) Artiach,Gonzalo et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1304572026-05-29T05:05:01Z
dc.title.none.fl_str_mv Opposing effects on vascular smooth muscle cell proliferation and macrophage-induced inflammation reveal a protective role for the proresolving lipid mediator receptor ChemR23 in intimal hyperplasia
title Opposing effects on vascular smooth muscle cell proliferation and macrophage-induced inflammation reveal a protective role for the proresolving lipid mediator receptor ChemR23 in intimal hyperplasia
spellingShingle Opposing effects on vascular smooth muscle cell proliferation and macrophage-induced inflammation reveal a protective role for the proresolving lipid mediator receptor ChemR23 in intimal hyperplasia
Artiach, Gonzalo
Inflamació
Múscul llis
Malalties vasculars
Inflammation
Smooth muscle
Vascular diseases
title_short Opposing effects on vascular smooth muscle cell proliferation and macrophage-induced inflammation reveal a protective role for the proresolving lipid mediator receptor ChemR23 in intimal hyperplasia
title_full Opposing effects on vascular smooth muscle cell proliferation and macrophage-induced inflammation reveal a protective role for the proresolving lipid mediator receptor ChemR23 in intimal hyperplasia
title_fullStr Opposing effects on vascular smooth muscle cell proliferation and macrophage-induced inflammation reveal a protective role for the proresolving lipid mediator receptor ChemR23 in intimal hyperplasia
title_full_unstemmed Opposing effects on vascular smooth muscle cell proliferation and macrophage-induced inflammation reveal a protective role for the proresolving lipid mediator receptor ChemR23 in intimal hyperplasia
title_sort Opposing effects on vascular smooth muscle cell proliferation and macrophage-induced inflammation reveal a protective role for the proresolving lipid mediator receptor ChemR23 in intimal hyperplasia
dc.creator.none.fl_str_mv Artiach, Gonzalo
Carracedo, Miguel
Clària i Enrich, Joan
Laguna Fernández, Andrés
Bäck, Magnus
author Artiach, Gonzalo
author_facet Artiach, Gonzalo
Carracedo, Miguel
Clària i Enrich, Joan
Laguna Fernández, Andrés
Bäck, Magnus
author_role author
author2 Carracedo, Miguel
Clària i Enrich, Joan
Laguna Fernández, Andrés
Bäck, Magnus
author2_role author
author
author
author
dc.subject.none.fl_str_mv Inflamació
Múscul llis
Malalties vasculars
Inflammation
Smooth muscle
Vascular diseases
topic Inflamació
Múscul llis
Malalties vasculars
Inflammation
Smooth muscle
Vascular diseases
description Intimal hyperplasia remains a significant clinical problem in for example coronary artery bypass graft failure. Since omega-3 fatty acids reduce intimal hyperplasia, we hypothesized that the G protein-coupled receptor ChemR23 for the omega-3-derived pro-resolving lipid mediator resolvin E1 drives those effects. ChemR23+/+ and ChemR23-/- mice were generated with or without introduction of the Caenorhabditis elegans fat-1 transgene, which leads to an endogenous omega-3 fatty acid synthesis and thus increasing the substrate for resolvin E1 formation. ChemR23 deletion significantly increased intimal hyperplasia 28 days after ligation of the left common carotid artery. Mice expressing the fat-1 transgene showed reduced intimal hyperplasia independently of ChemR23 expression. ChemR23-/- Vascular smooth muscle cells (VSMCs) exhibited a significantly lower proliferation compared with VSMCs derived from ChemR23+/+ mice. In contrast, ChemR23-/- peritoneal macrophages had significantly higher mRNA levels of pro-inflammatory cytokines compared with ChemR23+/+ macrophages. Finally, conditioned media (CM) transfer from ChemR23-/- macrophages to VSMCs significantly increased VSMC proliferation compared with CM from ChemR23+/+ macrophages. Taken together, these results point to a dual effect of ChemR23 in resolution pharmacology by directly stimulating VSMC proliferation and at the same time suppressing macrophage-induced VSMC proliferation. In conclusion, these differential effects of ChemR23 signaling in VSMC and macrophages open up a novel notion for intimal hyperplasia pathophysiology, where ChemR23-transduced effects on the vascular wall may vary, and even be opposing, depending on the degrees of resolution of inflammation.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/130457
url https://hdl.handle.net/2445/130457
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fphar.2018.01327
Frontiers in Pharmacology, 2018, vol. 9, p. 1327
https://doi.org/10.3389/fphar.2018.01327
dc.rights.none.fl_str_mv cc-by (c) Artiach,Gonzalo et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Artiach,Gonzalo et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 5 p.
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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