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dc.contributor.authorRamírez Carracedo, Rafael
dc.contributor.authorTesoro Santos, Laura 
dc.contributor.authorHernández, Ignacio
dc.contributor.authorDíez Mata, Javier
dc.contributor.authorFilice, Marco
dc.contributor.authorToro, Rocío
dc.contributor.authorRodríguez Piñero, Manuel
dc.contributor.authorZamorano, José Luis
dc.contributor.authorSaura, Marta
dc.contributor.authorZaragoza Sánchez, Carlos 
dc.date.accessioned2018-11-20T12:24:03Z
dc.date.available2018-11-20T12:24:03Z
dc.date.issued2018
dc.identifier.issn1422-0067spa
dc.identifier.urihttp://hdl.handle.net/10641/1528
dc.description.abstractLack of endothelial nitric oxide causes endothelial dysfunction and circulating monocyte infiltration, contributing to systemic atheroma plaque formation in arterial territories. Among the different inflammatory products, macrophage-derived foam cells and smooth muscle cells synthesize matrix metalloproteinases (MMPs), playing a pivotal role in early plaque formation and enlargement. We found increased levels of MMP-9 and MMP-13 in human endarterectomies with advanced atherosclerosis, together with significant amounts of extracellular matrix (ECM) metalloproteinase inducer EMMPRIN. To test whether the absence of NO may aggravate atherosclerosis through EMMPRIN activation, double NOS3/apoE knockout (KO) mice expressed high levels of EMMPRIN in carotid plaques, suggesting that targeting extracellular matrix degradation may represent a new mechanism by which endothelial NO prevents atherosclerosis. Based on our previous experience, by using gadolinium-enriched paramagnetic fluorescence micellar nanoparticles conjugated with AP9 (NAP9), an EMMPRIN-specific binding peptide, magnetic resonance sequences allowed non-invasive visualization of carotid EMMPRIN in NOS3/apoE over apoE control mice, in which atheroma plaques were significantly reduced. Taken together, these results point to EMMPRIN as a new therapeutic target of NO-mediated protection against atherosclerosis, and NAP9 as a non-invasive molecular tool to target atherosclerosis.spa
dc.language.isoengspa
dc.publisherInternational Journal of Molecular Sciencesspa
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subjectNitric oxidespa
dc.subjectMetalloproteinsasesspa
dc.subjectNanoparticlesspa
dc.subjectMagnetic resonance imagingspa
dc.titleNon-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide.spa
dc.typejournal articlespa
dc.type.hasVersionAMspa
dc.rights.accessRightsopen accessspa
dc.description.extent2309 KBspa
dc.identifier.doi10.3390/ijms19103248spa


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