A major role for RCAN1 in atherosclerosis progression

Atherosclerosis is a complex inflammatory disease involving extensive vascular vessel remodelling and migration of vascular cells. As RCAN1 is implicated in cell migration, we investigated its contribution to atherosclerosis. We show RCAN1 induction in atherosclerotic human and mouse tissues. Rcan1...

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Autores: Mendez-Barbero, N, Esteban, V, Villahoz, S, Escolano, A, Urso, K, Alfranca, A, Rodriguez, C, Sanchez, SA, Osawa, T, Andres, V, Martinez-Gonzalez, J, Minami, T, Redondo, JM, Campanero, MR
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p10057
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10057
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84897005459&doi=10.1002%2femmm.201302842&partnerID=40&md5=b94df75edb77dea7d5c7cf4d702f2277
Access Level:acceso abierto
Palabra clave:CD36 antigen
gelatinase A
gelatinase B
interleukin 10
mannose receptor
oxidized low density lipoprotein
protein
protein rcan 1
unclassified drug
animal experiment
animal model
animal tissue
antigen expression
antigen presentation
aorta arch
aorta sinus
aorta valve disease
article
ascending aorta
atherogenesis
atheroma
atherosclerosis
atherosclerotic plaque
chemotaxis
comparative study
controlled study
coronary artery
disease course
disease severity
endothelium cell
gene inactivation
genotype
hematopoietic cell
hematopoietic stem cell
human
human tissue
internal mammary artery
lipid storage
macrophage
macrophage migration
mouse
nonhuman
peritoneum macrophage
phenotype
priority journal
protein expression
smooth muscle fiber
upregulation
vascular smooth muscle
hypercholesterolemia
inflammation
RCAN1
Aneurysm
Animals
Antigens, CD36
Apolipoproteins E
Atherosclerosis
Bone Marrow Cells
Bone Marrow Transplan
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repository_id_str
spelling A major role for RCAN1 in atherosclerosis progressionMendez-Barbero, NEsteban, VVillahoz, SEscolano, AUrso, KAlfranca, ARodriguez, CSanchez, SAOsawa, TAndres, VMartinez-Gonzalez, JMinami, TRedondo, JMCampanero, MRCD36 antigengelatinase Agelatinase Binterleukin 10mannose receptoroxidized low density lipoproteinproteinprotein rcan 1unclassified druganimal experimentanimal modelanimal tissueantigen expressionantigen presentationaorta archaorta sinusaorta valve diseasearticleascending aortaatherogenesisatheromaatherosclerosisatherosclerotic plaquechemotaxiscomparative studycontrolled studycoronary arterydisease coursedisease severityendothelium cellgene inactivationgenotypehematopoietic cellhematopoietic stem cellhumanhuman tissueinternal mammary arterylipid storagemacrophagemacrophage migrationmousenonhumanperitoneum macrophagephenotypepriority journalprotein expressionsmooth muscle fiberupregulationvascular smooth muscleatherosclerosishypercholesterolemiainflammationmacrophageRCAN1AneurysmAnimalsAntigens, CD36Apolipoproteins EAtherosclerosisBone Marrow CellsBone Marrow TransplanAtherosclerosis is a complex inflammatory disease involving extensive vascular vessel remodelling and migration of vascular cells. As RCAN1 is implicated in cell migration, we investigated its contribution to atherosclerosis. We show RCAN1 induction in atherosclerotic human and mouse tissues. Rcan1 was expressed in lesional macrophages, endothelial cells and vascular smooth muscle cells and was induced by treatment of these cells with oxidized LDLs (oxLDLs). Rcan1 regulates CD36 expression and its genetic inactivation reduced atherosclerosis extension and severity in Apoe-/- mice. This effect was mechanistically linked to diminished oxLDL uptake, resistance to oxLDL-mediated inhibition of macrophage migration and increased lesional IL-10 and mannose receptor expression. Moreover, Apoe-/-Rcan1-/- macrophages expressed higher-than-Apoe-/- levels of anti-inflammatory markers. We previously showed that Rcan1 mediates aneurysm development and that its expression is not required in haematopoietic cells for this process. However, transplantation of Apoe-/-Rcan1-/- bone-marrow (BM) cells into Apoe-/- recipients confers atherosclerosis resistance. Our data define a major role for haematopoietic Rcan1 in atherosclerosis and suggest that therapies aimed at inhibiting RCAN1 expression or function might significantly reduce atherosclerosis burden. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.WILEY2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10057https://www.scopus.com/inward/record.uri?eid=2-s2.0-84897005459&doi=10.1002%2femmm.201302842&partnerID=40&md5=b94df75edb77dea7d5c7cf4d702f2277EMBO Molecular MedicineISSN: 17574676ISSNe: 17574684reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p100572026-06-14T12:41:47Z
dc.title.none.fl_str_mv A major role for RCAN1 in atherosclerosis progression
title A major role for RCAN1 in atherosclerosis progression
spellingShingle A major role for RCAN1 in atherosclerosis progression
Mendez-Barbero, N
CD36 antigen
gelatinase A
gelatinase B
interleukin 10
mannose receptor
oxidized low density lipoprotein
protein
protein rcan 1
unclassified drug
animal experiment
animal model
animal tissue
antigen expression
antigen presentation
aorta arch
aorta sinus
aorta valve disease
article
ascending aorta
atherogenesis
atheroma
atherosclerosis
atherosclerotic plaque
chemotaxis
comparative study
controlled study
coronary artery
disease course
disease severity
endothelium cell
gene inactivation
genotype
hematopoietic cell
hematopoietic stem cell
human
human tissue
internal mammary artery
lipid storage
macrophage
macrophage migration
mouse
nonhuman
peritoneum macrophage
phenotype
priority journal
protein expression
smooth muscle fiber
upregulation
vascular smooth muscle
atherosclerosis
hypercholesterolemia
inflammation
macrophage
RCAN1
Aneurysm
Animals
Antigens, CD36
Apolipoproteins E
Atherosclerosis
Bone Marrow Cells
Bone Marrow Transplan
title_short A major role for RCAN1 in atherosclerosis progression
title_full A major role for RCAN1 in atherosclerosis progression
title_fullStr A major role for RCAN1 in atherosclerosis progression
title_full_unstemmed A major role for RCAN1 in atherosclerosis progression
title_sort A major role for RCAN1 in atherosclerosis progression
dc.creator.none.fl_str_mv Mendez-Barbero, N
Esteban, V
Villahoz, S
Escolano, A
Urso, K
Alfranca, A
Rodriguez, C
Sanchez, SA
Osawa, T
Andres, V
Martinez-Gonzalez, J
Minami, T
Redondo, JM
Campanero, MR
author Mendez-Barbero, N
author_facet Mendez-Barbero, N
Esteban, V
Villahoz, S
Escolano, A
Urso, K
Alfranca, A
Rodriguez, C
Sanchez, SA
Osawa, T
Andres, V
Martinez-Gonzalez, J
Minami, T
Redondo, JM
Campanero, MR
author_role author
author2 Esteban, V
Villahoz, S
Escolano, A
Urso, K
Alfranca, A
Rodriguez, C
Sanchez, SA
Osawa, T
Andres, V
Martinez-Gonzalez, J
Minami, T
Redondo, JM
Campanero, MR
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CD36 antigen
gelatinase A
gelatinase B
interleukin 10
mannose receptor
oxidized low density lipoprotein
protein
protein rcan 1
unclassified drug
animal experiment
animal model
animal tissue
antigen expression
antigen presentation
aorta arch
aorta sinus
aorta valve disease
article
ascending aorta
atherogenesis
atheroma
atherosclerosis
atherosclerotic plaque
chemotaxis
comparative study
controlled study
coronary artery
disease course
disease severity
endothelium cell
gene inactivation
genotype
hematopoietic cell
hematopoietic stem cell
human
human tissue
internal mammary artery
lipid storage
macrophage
macrophage migration
mouse
nonhuman
peritoneum macrophage
phenotype
priority journal
protein expression
smooth muscle fiber
upregulation
vascular smooth muscle
atherosclerosis
hypercholesterolemia
inflammation
macrophage
RCAN1
Aneurysm
Animals
Antigens, CD36
Apolipoproteins E
Atherosclerosis
Bone Marrow Cells
Bone Marrow Transplan
topic CD36 antigen
gelatinase A
gelatinase B
interleukin 10
mannose receptor
oxidized low density lipoprotein
protein
protein rcan 1
unclassified drug
animal experiment
animal model
animal tissue
antigen expression
antigen presentation
aorta arch
aorta sinus
aorta valve disease
article
ascending aorta
atherogenesis
atheroma
atherosclerosis
atherosclerotic plaque
chemotaxis
comparative study
controlled study
coronary artery
disease course
disease severity
endothelium cell
gene inactivation
genotype
hematopoietic cell
hematopoietic stem cell
human
human tissue
internal mammary artery
lipid storage
macrophage
macrophage migration
mouse
nonhuman
peritoneum macrophage
phenotype
priority journal
protein expression
smooth muscle fiber
upregulation
vascular smooth muscle
atherosclerosis
hypercholesterolemia
inflammation
macrophage
RCAN1
Aneurysm
Animals
Antigens, CD36
Apolipoproteins E
Atherosclerosis
Bone Marrow Cells
Bone Marrow Transplan
description Atherosclerosis is a complex inflammatory disease involving extensive vascular vessel remodelling and migration of vascular cells. As RCAN1 is implicated in cell migration, we investigated its contribution to atherosclerosis. We show RCAN1 induction in atherosclerotic human and mouse tissues. Rcan1 was expressed in lesional macrophages, endothelial cells and vascular smooth muscle cells and was induced by treatment of these cells with oxidized LDLs (oxLDLs). Rcan1 regulates CD36 expression and its genetic inactivation reduced atherosclerosis extension and severity in Apoe-/- mice. This effect was mechanistically linked to diminished oxLDL uptake, resistance to oxLDL-mediated inhibition of macrophage migration and increased lesional IL-10 and mannose receptor expression. Moreover, Apoe-/-Rcan1-/- macrophages expressed higher-than-Apoe-/- levels of anti-inflammatory markers. We previously showed that Rcan1 mediates aneurysm development and that its expression is not required in haematopoietic cells for this process. However, transplantation of Apoe-/-Rcan1-/- bone-marrow (BM) cells into Apoe-/- recipients confers atherosclerosis resistance. Our data define a major role for haematopoietic Rcan1 in atherosclerosis and suggest that therapies aimed at inhibiting RCAN1 expression or function might significantly reduce atherosclerosis burden. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.
publishDate 2013
dc.date.none.fl_str_mv 2013
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://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10057
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84897005459&doi=10.1002%2femmm.201302842&partnerID=40&md5=b94df75edb77dea7d5c7cf4d702f2277
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10057
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84897005459&doi=10.1002%2femmm.201302842&partnerID=40&md5=b94df75edb77dea7d5c7cf4d702f2277
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv EMBO Molecular Medicine
ISSN: 17574676
ISSNe: 17574684
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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repository.mail.fl_str_mv
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