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00925njm 22002777a 4500 dc Ramirez-Carracedo, Rafael author Tesoro, Laura author Hernandez, Ignacio author Diez-Mata, Javier author Filice, Marco author Toro, Rocio author Rodriguez-Pinero, Manuel author Luis Zamorano, Jose author Saura, Marta author Zaragoza, Carlos author 2018 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. Int J Mol Sci. 2018; 19(10):E3248 10.3390/ijms19103248 1422-0067 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 30347750 http://hdl.handle.net/20.500.12105/6663 Nitric oxide Endothelial nitric oxide synthase Metalloproteinsases Nanoparticles Magnetic resonance imaging Extacellular matrix metalloproteinase inducer EMMPRIN CELL-SURFACE EXPRESSION IN-VIVO LIGAND CYCLOPHILIN CD147 MMP-9 CD147/EMMPRIN CAVEOLIN-1 ADHESION DISEASE MICE Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide