Nitric Oxide Induces the Progression of Abdominal Aortic Aneurysms through the Matrix Metalloproteinase Inducer EMMPRIN

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dc.contributor.authorLizarbe, Tania
dc.contributor.authorTarín, Carlos
dc.contributor.authorGómez, Mónica
dc.contributor.authorLavín Plaza, Begoña
dc.contributor.authorAracil Ávila, Enrique
dc.contributor.authorOrte, Luis
dc.contributor.authorZaragoza, Carlos
dc.date.accessioned2024-01-30T13:49:37Z
dc.date.available2024-01-30T13:49:37Z
dc.date.issued2009
dc.description.abstractNitric Oxide (NO) is involved in the development and progression of abdominal aortic aneurysms (AAA). We found that inhibition of inducible NO synthase (iNOS) protects mice in an elastase-induced AAA model, significantly inhibiting the production of matrix metalloproteinase-13 (MMP-13). The extracellular MMP inducer (EMMPRIN; CD147) was increased in human AAA biopsies and in wild-type murine AAA but not in AAA from iNOS null mice. In cells overexpressing ectopic EMMPRIN, MMP-13 secretion was stimulated, whereas silencing of EMMPRIN by RNA interference led to significant inhibition of MMP-13 expression. In addition, elastase infusion of MMP-13 null mouse aortas induced a significant increase of EMMPRIN but reduced aortic dilatation when compared with wild-type mice, suggesting that NO-mediated AAA may be mediated through EMMPRIN induction of MMP-13. These findings were further verified in elastase-infused iNOS null mice, in which daily administration of NO caused a significant aortic dilatation and the expression of EMMPRIN and MMP-13. By contrast, in iNOS wild-type mice, pharmacological inhibition of iNOS by administration of 1400 W induced a reduction of aortic diameter and inhibition of MMP-13 and EMMPRIN expression when compared with control mice. Our results suggest that NO may regulate the development of AAA in part by inducing the expression of EMMPRIN and modulating the activity of MMP-13 in murine and human aneurysms.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Ciencias Químicas
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationLizarbe, Tania R., et al. «Nitric Oxide Induces the Progression of Abdominal Aortic Aneurysms through the Matrix Metalloproteinase Inducer EMMPRIN». The American Journal of Pathology, vol. 175, n.o 4, octubre de 2009, pp. 1421-30. https://doi.org/10.2353/ajpath.2009.080845.
dc.identifier.doi10.2353/ajpath.2009.080845
dc.identifier.issn0002-9440
dc.identifier.officialurlhttps://doi.org/10.2353/ajpath.2009.080845
dc.identifier.relatedurlhttps://www.sciencedirect.com/science/article/pii/S0002944010606542
dc.identifier.urihttps://hdl.handle.net/20.500.14352/96589
dc.issue.number4
dc.journal.titleThe American Journal of Pathology
dc.language.isoeng
dc.publisherAmerican Society for Investigative Pathology
dc.rights.accessRightsrestricted access
dc.subject.cdu577.1
dc.subject.ucmBioquímica (Química)
dc.subject.unesco24 Ciencias de la Vida
dc.titleNitric Oxide Induces the Progression of Abdominal Aortic Aneurysms through the Matrix Metalloproteinase Inducer EMMPRIN
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number175
dspace.entity.typePublication
relation.isAuthorOfPublication1f5cced3-0761-429d-a70e-4881fff2f7a9
relation.isAuthorOfPublication779931d3-ee0a-4e5a-a374-3e9978ed060b
relation.isAuthorOfPublication.latestForDiscovery1f5cced3-0761-429d-a70e-4881fff2f7a9
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