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dc.contributor.author | Silvestre-Roig, Carlos | |
dc.contributor.author | Fernandez, Patricia | |
dc.contributor.author | Esteban, Vanesa | |
dc.contributor.author | Pello, Oscar M | |
dc.contributor.author | Indolfi, Ciro | |
dc.contributor.author | Rodriguez, Cristina | |
dc.contributor.author | Rodríguez-Calvo, Ricardo | |
dc.contributor.author | Lopez-Maderuelo, Dolores | |
dc.contributor.author | Bauriedel, Gerhard | |
dc.contributor.author | Hutter, Randolph | |
dc.contributor.author | Fuster, Valentin | |
dc.contributor.author | Ibáñez, Borja | |
dc.contributor.author | Redondo, Juan Miguel | |
dc.contributor.author | Martinez-Gonzalez, Jose | |
dc.contributor.author | Andres, Vicente | |
dc.date.accessioned | 2019-06-06T10:31:26Z | |
dc.date.available | 2019-06-06T10:31:26Z | |
dc.date.issued | 2013-05 | |
dc.identifier.citation | Arterioscler Thromb Vasc Biol. 2013; 33(5):1036-45 | es_ES |
dc.identifier.issn | 1079-5642 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/7748 | |
dc.description.abstract | OBJECTIVE: Atherosclerosis and restenosis are multifactorial diseases associated with abnormal vascular smooth muscle cell (VSMC) proliferation. Nuclear factor-Y (NF-Y) plays a major role in transcriptional activation of the CYCLIN B1 gene (CCNB1), a key positive regulator of cell proliferation and neointimal thickening. Here, we investigated the role of NF-Y in occlusive vascular disease. APPROACH AND RESULTS: We performed molecular and expression studies in cultured cells, animal models, and human tissues. We find upregulation of NF-Y and cyclin B1 expression in proliferative regions of murine atherosclerotic plaques and mechanically induced lesions, which correlates with higher binding of NF-Y to target sequences in the CCNB1 promoter. NF-YA expression in neointimal lesions is detected in VSMCs, macrophages, and endothelial cells. Platelet-derived growth factor-BB, a main inductor of VSMC growth and neointima development, induces the recruitment of NF-Y to the CCNB1 promoter and augments both CCNB1 mRNA expression and cell proliferation through extracellular signal-regulated kinase 1/2 and Akt activation in rat and human VSMCs. Moreover, adenovirus-mediated overexpression of a NF-YA-dominant negative mutant inhibits platelet-derived growth factor-BB-induced CCNB1 expression and VSMC proliferation in vitro and neointimal lesion formation in a mouse model of femoral artery injury. We also detect NF-Y expression and DNA-binding activity in human neointimal lesions. CONCLUSIONS: Our results identify NF-Y as a key downstream effector of the platelet-derived growth factor-BB-dependent mitogenic pathway that is activated in experimental and human vasculoproliferative diseases. They also identify NF-Y inhibition as a novel and attractive strategy for the local treatment of neointimal formation induced by vessel denudation. | es_ES |
dc.description.sponsorship | This study was funded by the Spanish Ministry of Economy and Competiveness (MINECO; grants SAF2010-16044, SAF200911949), Instituto de Salud Carlos III (ISCIII; grants RD12/0042/0021, RD12/0042/0028, RD12/0042/0053), and the Dr Léon Dumont Prize 2010 by the Belgian Society of Cardiology (to Vicente Andrés). Patricia Fernández received salary support from ISCIII and Carlos Silvestre-Roig from Fundación Mario Losantos del Campo and Fundación Ferrer para la Investigación. Óscar M. Pello and Ricardo Rodríguez-Calvo hold a Juan de la Cierva contract from MINECO. Vanesa Esteban is an investigator of the Sara Borell program from ISCIII (CD06/00232). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by MINECO and Pro-CNIC Foundation. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Heart Association (AHA) | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Apolipoproteins E | es_ES |
dc.subject.mesh | Atherosclerosis | es_ES |
dc.subject.mesh | Becaplermin | es_ES |
dc.subject.mesh | CCAAT-Binding Factor | es_ES |
dc.subject.mesh | Cell Proliferation | es_ES |
dc.subject.mesh | Cells, Cultured | es_ES |
dc.subject.mesh | Cyclin B1 | es_ES |
dc.subject.mesh | Endothelial Cells | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Male | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Inbred C57BL | es_ES |
dc.subject.mesh | Muscle, Smooth, Vascular | es_ES |
dc.subject.mesh | Neointima | es_ES |
dc.subject.mesh | Proto-Oncogene Proteins c-sis | es_ES |
dc.subject.mesh | Rats | es_ES |
dc.subject.mesh | Rats, Wistar | es_ES |
dc.title | Inactivation of nuclear factor-Y inhibits vascular smooth muscle cell proliferation and neointima formation | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 23430616 | es_ES |
dc.format.volume | 33 | es_ES |
dc.format.number | 5 | es_ES |
dc.format.page | 1036-45 | es_ES |
dc.identifier.doi | 10.1161/ATVBAHA.112.300580 | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Belgian Society of Cardiology | |
dc.contributor.funder | Fundación Mario Losantos del Campo | |
dc.contributor.funder | Fundación Ferrer para la Investigación | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1524-4636 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1161/ATVBAHA.112.300580 | es_ES |
dc.identifier.journal | Arteriosclerosis, thrombosis, and vascular biology | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genética | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Imagen Cardiovascular y Estudios Poblacionales | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Laboratorio Traslacional para la Imagen y Terapia Cardiovascular | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Regulación Génica en Remodelado Vascular e Inflamación | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2010-16044 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2009-11949 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD12/0042/0021 | 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 |