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dc.creatorBermúdez Pulgarín, Beatrizes
dc.creatorMedina, Indiraes
dc.creatorCougoule, Célibees
dc.creatorDrechsler, Maikes
dc.creatorSluimer, Judithes
dc.date.accessioned2019-02-04T11:14:44Z
dc.date.available2019-02-04T11:14:44Z
dc.date.issued2015
dc.identifier.citationBermúdez Pulgarín, B., Medina, I., Cougoule, C., Drechsler, M. y Sluimer, J. (2015). Hck/Fgr Kinase Deficiency Reduces Plaque Growth and Stability by Blunting Monocyte Recruitment and Intraplaque Motility. Circulation, 132 (6), 490-501.
dc.identifier.issn1524-4539es
dc.identifier.urihttps://hdl.handle.net/11441/82431
dc.description.abstractBackground Leukocyte migration is critical for the infiltration of monocytes and accumulation of monocyte derived macrophages in inflammation. Considering that Hck and Fgr are instrumental in this process, their impact on atherosclerosis and on lesion inflammation and stability was evaluated. Methods and Results Hematopoietic Hck/Fgr–deficient, LDLr−/− chimeras, obtained by bone marrow transplantation, had smaller but, paradoxically, less stable lesions with reduced macrophage content, overt cap thinning, and necrotic core expansion as most prominent features. Despite a Ly6Chigh skewed proinflammatory monocyte phenotype, Hck/Fgr deficiency led to disrupted adhesion of myeloid cells to and transmigration across endothelial monolayers in-vitro and atherosclerotic plaques in–vivo, as assessed by intravital microscopy, flow cytometry and histological examination of atherosclerotic arteries. Moreover, Hck/Fgr deficient macrophages showed blunted podosome formation and mesenchymal migration capacity. In consequence transmigrated dKO macrophages were seen to accumulate in the fibrous cap, potentially promoting its focal erosion, as observed for dKO chimeras. Conclusions Hematopoietic deficiency of Hck and Fgr led to attenuated atherosclerotic plaque formation by abrogating endothelial adhesion and transmigration; paradoxically it also promoted plaque instability by causing monocyte subset imbalance and subendothelial accumulation, raising a note of caution regarding src kinase targeted intervention in plaque inflammation.es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherAmerican Heart Associationes
dc.relation.ispartofCirculation, 132 (6), 490-501.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectkinaseses
dc.subjectmobilityes
dc.subjectatherosclerosises
dc.subjectimmunologyes
dc.subjectleukocytees
dc.subjectmigrationes
dc.subjectplaque progressiones
dc.titleHck/Fgr Kinase Deficiency Reduces Plaque Growth and Stability by Blunting Monocyte Recruitment and Intraplaque Motilityes
dc.typeinfo:eu-repo/semantics/articlees
dc.type.versioninfo:eu-repo/semantics/acceptedVersiones
dc.rights.accessrightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Farmacologíaes
dc.relation.publisherversionhttp://dx.doi.org/10.1161/CIRCULATIONAHA.114.012316es
dc.identifier.doi10.1161/CIRCULATIONAHA.114.012316es
idus.format.extent11 p.es
dc.journaltitleCirculationes
dc.publication.volumen132es
dc.publication.issue6es
dc.publication.initialPage490es
dc.publication.endPage501es

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