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Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide

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 metall...

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Autores principales: Ramirez-Carracedo, Rafael, Tesoro, Laura, Hernandez, Ignacio, Diez-Mata, Javier, Filice, Marco, Toro, Rocío, Rodriguez-Piñero, Manuel, Zamorano, Jose Luis, Saura, Marta, Zaragoza, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214015/
https://www.ncbi.nlm.nih.gov/pubmed/30347750
http://dx.doi.org/10.3390/ijms19103248
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author Ramirez-Carracedo, Rafael
Tesoro, Laura
Hernandez, Ignacio
Diez-Mata, Javier
Filice, Marco
Toro, Rocío
Rodriguez-Piñero, Manuel
Zamorano, Jose Luis
Saura, Marta
Zaragoza, Carlos
author_facet Ramirez-Carracedo, Rafael
Tesoro, Laura
Hernandez, Ignacio
Diez-Mata, Javier
Filice, Marco
Toro, Rocío
Rodriguez-Piñero, Manuel
Zamorano, Jose Luis
Saura, Marta
Zaragoza, Carlos
author_sort Ramirez-Carracedo, Rafael
collection PubMed
description 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.
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spelling pubmed-62140152018-11-14 Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide Ramirez-Carracedo, Rafael Tesoro, Laura Hernandez, Ignacio Diez-Mata, Javier Filice, Marco Toro, Rocío Rodriguez-Piñero, Manuel Zamorano, Jose Luis Saura, Marta Zaragoza, Carlos Int J Mol Sci Article 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. MDPI 2018-10-19 /pmc/articles/PMC6214015/ /pubmed/30347750 http://dx.doi.org/10.3390/ijms19103248 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ramirez-Carracedo, Rafael
Tesoro, Laura
Hernandez, Ignacio
Diez-Mata, Javier
Filice, Marco
Toro, Rocío
Rodriguez-Piñero, Manuel
Zamorano, Jose Luis
Saura, Marta
Zaragoza, Carlos
Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide
title Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide
title_full Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide
title_fullStr Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide
title_full_unstemmed Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide
title_short Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide
title_sort non-invasive detection of extracellular matrix metalloproteinase inducer emmprin, a new therapeutic target against atherosclerosis, inhibited by endothelial nitric oxide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214015/
https://www.ncbi.nlm.nih.gov/pubmed/30347750
http://dx.doi.org/10.3390/ijms19103248
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