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dc.contributor.author | Mendez-Barbero, Nerea | |
dc.contributor.author | Esteban, Vanesa | |
dc.contributor.author | Villahoz, Silvia | |
dc.contributor.author | Escolano, Amelia | |
dc.contributor.author | Urso, Katia | |
dc.contributor.author | Alfranca, Arantzazu | |
dc.contributor.author | Rodriguez, Cristina | |
dc.contributor.author | Sanchez, Susana A | |
dc.contributor.author | Osawa, Tsuyoshi | |
dc.contributor.author | Andres, Vicente | |
dc.contributor.author | Martinez-Gonzalez, Jose | |
dc.contributor.author | Minami, Takashi | |
dc.contributor.author | Redondo, Juan Miguel | |
dc.contributor.author | Campanero, Miguel R | |
dc.date.accessioned | 2019-05-14T10:00:50Z | |
dc.date.available | 2019-05-14T10:00:50Z | |
dc.date.issued | 2013-12 | |
dc.identifier.citation | EMBO Mol Med. 2013; 5(12):1901-17 | es_ES |
dc.identifier.issn | 17574676 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/7569 | |
dc.description.abstract | 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. | es_ES |
dc.description.sponsorship | The Spanish Ministry of Economy and Competitiveness (Ministerio de Economía y Competitividad) supports MRC, JMR and JM‐G with grants SAF2010‐15126, SAF2009‐10708 and SAF2012‐40127, respectively; MRC is also supported by the Spanish Council for Scientific Research (CSIC); JMR is also supported by Fundación La Marató TV3 (080731), and Fundación Genoma España (GENOMA). The Red de Investigacion Cardiovascular (RIC) of the Spanish Ministry of Health (Ministerio de Sanidad) supports the research of JMR, VA and JM‐G with grants RD12/0042/0022, RD12/0042/0028 and RD12/0042/0053, respectively. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Economy and Competitiveness and the Pro‐CNIC Foundation. TM was supported in part by the Leading‐edge Research Promotion Fund (LS038, TM). VE was an investigator of the Sara Borrell Program (CD06/ 00232), and NM‐B holds an FPU fellowship (FPU2008‐1500). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | EMBO Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | RCAN1 | es_ES |
dc.subject | atherosclerosis | es_ES |
dc.subject | hypercholesterolemia | es_ES |
dc.subject | inflammation | es_ES |
dc.subject | macrophage | es_ES |
dc.subject.mesh | Aneurysm | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Apolipoproteins E | es_ES |
dc.subject.mesh | Atherosclerosis | es_ES |
dc.subject.mesh | Bone Marrow Cells | es_ES |
dc.subject.mesh | Bone Marrow Transplantation | es_ES |
dc.subject.mesh | CD36 Antigens | es_ES |
dc.subject.mesh | Cell Movement | es_ES |
dc.subject.mesh | Disease Progression | es_ES |
dc.subject.mesh | Endothelial Cells | es_ES |
dc.subject.mesh | Foam Cells | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Intracellular Signaling Peptides and Proteins | es_ES |
dc.subject.mesh | Lipoproteins, LDL | es_ES |
dc.subject.mesh | Macrophages | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Knockout | es_ES |
dc.subject.mesh | Muscle Proteins | es_ES |
dc.subject.mesh | Muscle, Smooth, Vascular | es_ES |
dc.subject.mesh | Phenotype | es_ES |
dc.title | A major role for RCAN1 in atherosclerosis progression | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 24127415 | es_ES |
dc.format.volume | 5 | es_ES |
dc.format.number | 12 | es_ES |
dc.format.page | 1901-17 | es_ES |
dc.identifier.doi | 10.1002/emmm.201302842 | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Consejo Superior de Investigaciones Científicas (España) | |
dc.contributor.funder | Fundación Genoma España | |
dc.contributor.funder | Fundación ProCNIC | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1757-4684 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1002/emmm.201302842 | es_ES |
dc.identifier.journal | EMBO molecular medicine | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Regulación Génica en Remodelado Vascular e Inflamación | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genética | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2010‐15126 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2009‐10708 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2012‐40127 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD12/0042/0022 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD12/0042/0028 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD12/0042/0053 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/CD06/00232 | es_ES |
dc.rights.accessRights | open access | es_ES |