dc.contributor.author | Ramirez-Carracedo, Rafael | |
dc.contributor.author | Tesoro, Laura | |
dc.contributor.author | Hernandez, Ignacio | |
dc.contributor.author | Diez-Mata, Javier | |
dc.contributor.author | Filice, Marco | |
dc.contributor.author | Toro, Rocio | |
dc.contributor.author | Rodriguez-Pinero, Manuel | |
dc.contributor.author | Luis Zamorano, Jose | |
dc.contributor.author | Saura, Marta | |
dc.contributor.author | Zaragoza, Carlos | |
dc.date.accessioned | 2018-11-22T08:10:50Z | |
dc.date.available | 2018-11-22T08:10:50Z | |
dc.date.issued | 2018 | |
dc.identifier | ISI:000448951000403 | |
dc.identifier.citation | Int J Mol Sci. 2018; 19(10):E3248 | |
dc.identifier.issn | 1422-0067 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6663 | |
dc.description.abstract | Lack 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. | |
dc.description.sponsorship | This research was funded by (CZ) ``Instituto de Salud Carlos III, PI14/02022 (Plan Estatal de I+ D+ i 2013-2016) co-financed by the European Development Regional Fund A way to achieve Europe (ERDF)´´ and ``Universidad Francisco de Vitoria 2014, 2015, and 2016´´. (MF) ``Comunidad Autonoma de Madrid 2017-T1/BIO-4992. Atraccion de Talento´´ and ``Universidad Complutense de Madrid and the I + D collaborative Programme in Biomedicine NIETO-CM (B2017-BMD3731)´´. | |
dc.language.iso | eng | |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Nitric oxide | |
dc.subject | Endothelial nitric oxide synthase | |
dc.subject | Metalloproteinsases | |
dc.subject | Nanoparticles | |
dc.subject | Magnetic resonance imaging | |
dc.subject | Extacellular matrix metalloproteinase inducer EMMPRIN | |
dc.subject | CELL-SURFACE EXPRESSION | |
dc.subject | IN-VIVO | |
dc.subject | LIGAND CYCLOPHILIN | |
dc.subject | CD147 | |
dc.subject | MMP-9 | |
dc.subject | CD147/EMMPRIN | |
dc.subject | CAVEOLIN-1 | |
dc.subject | ADHESION | |
dc.subject | DISEASE | |
dc.subject | MICE | |
dc.title | Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 30347750 | |
dc.format.volume | 19 | |
dc.identifier.doi | 10.3390/ijms19103248 | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Complutense University of Madrid (España) | |
dc.contributor.funder | Francisco de Vitoria University (España) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.3390/ijms19103248 | |
dc.identifier.journal | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI14/02022 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/2017-T1/BIO-4992 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/B2017-BMD3731 | es_ES |
dc.rights.accessRights | open access | es_ES |