RT journal article
T1 Non-invasive detection of extracellular matrix metalloproteinase inducer EMMPRIN, a new therapeutic target against atherosclerosis, inhibited by endothelial nitric oxide
A1 Ramirez Carracedo, Rafael
A1 Tesoro, Laura
A1 Hernandez, Ignacio
A1 Diez Mata, Javier
A1 Filice, Marco
A1 Toro Cebada, Rocío
A1 Rodriguez Piñero, Manuel
A1 Zamorano, Jose Luis
A1 Saura, Marta
A1 Zaragoza, Carlos
A2 Cirugía
A2 Medicina
K1 nitric oxide
K1 endothelial nitric oxide synthase
K1 metalloproteinsases
K1 nanoparticles
K1 magnetic resonance imaging
K1 extacellular matrix metalloproteinase inducer EMMPRIN
AB Lack of endothelial nitric oxide causes endothelial dysfunction and circulating monocyteinfiltration, contributing to systemic atheroma plaque formation in arterial territories. Among thedifferent inflammatory products, macrophage-derived foam cells and smooth muscle cells synthesizematrix 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 advancedatherosclerosis, together with significant amounts of extracellular matrix (ECM) metalloproteinaseinducer EMMPRIN. To test whether the absence of NO may aggravate atherosclerosis throughEMMPRIN activation, double NOS3/apoE knockout (KO) mice expressed high levels of EMMPRINin carotid plaques, suggesting that targeting extracellular matrix degradation may represent a newmechanism 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-invasivevisualization of carotid EMMPRIN in NOS3/apoE over apoE control mice, in which atheroma plaqueswere significantly reduced. Taken together, these results point to EMMPRIN as a new therapeutictarget of NO-mediated protection against atherosclerosis, and NAP9 as a non-invasive molecular toolto target atherosclerosis.
PB MDPI
SN 1422-0067
YR 2018
FD 2018
LK http://hdl.handle.net/10498/32963
UL http://hdl.handle.net/10498/32963
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 09-may-2026