Functional interplay between endothelial nitric oxide synthase and membrane type 1–matrix metalloproteinase in migrating endothelial cells

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dc.contributor.authorGenís, Laura
dc.contributor.authorGonzalo, Pilar
dc.contributor.authorTutor, Antonio S.
dc.contributor.authorGálvez, Beatriz G.
dc.contributor.authorMartínez Ruiz, Antonio
dc.contributor.authorZaragoza, Carlos
dc.contributor.authorLamas, Santiago
dc.contributor.authorTryggvason, Karl
dc.contributor.authorApte, Suneel S.
dc.contributor.authorArroyo, Alicia G.
dc.date.accessioned2024-04-05T11:05:16Z
dc.date.available2024-04-05T11:05:16Z
dc.date.issued2007-10-15
dc.description.abstractNitric oxide (NO) is essential for vascular homeostasis and is also a critical modulator of angiogenesis; however, the molecular mechanisms of NO action during angiogenesis remain elusive. We have investigated the potential relationship between NO and membrane type 1–matrix metalloproteinase (MT1-MMP) during endothelial migration and capillary tube formation. Endothelial NO synthase (eNOS) colocalizes with MT1-MMP at motilityassociated structures in migratory human endothelial cells (ECs); moreover, NO is produced at these structures and is released into the medium during EC migration. We have therefore addressed 2 questions: (1) the putative regulation of MT1-MMP by NO in migratory ECs; and (2) the requirement for MT1-MMP in NOinduced EC migration and tube formation. NO upregulates MT1-MMP membrane clustering on migratory human ECs, and this is accompanied by increased degradation of type I collagen substrate. MT1-MMP membrane expression and localization are impaired in lung ECs from eNOS-deficient mice, and these cells also show impaired migration and tube formation in vitro. Inhibition of MT1-MMP with a neutralizing antibody impairs NOinduced tube formation by human ECs, and NO-induced endothelial migration and tube formation are impaired in lung ECs from mice deficient in MT1-MMP. MT1-MMP thus appears to be a key molecular effector of NO during the EC migration and angiogenic processes, and is a potential therapeutic target for NO-associated vascular disorders.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipComunidad Autónoma de Madrid
dc.description.sponsorshipMinisterio de Sanidad y Consumo
dc.description.sponsorshipMinisterio de Educación y Ciencia
dc.description.statuspub
dc.identifier.doi10.1182/blood-2007-01-068080
dc.identifier.issn0006-4971
dc.identifier.issn1528-0020
dc.identifier.officialurlhttps://ashpublications.org/blood/article/110/8/2916/23981/Functional-interplay-between-endothelial-nitric
dc.identifier.urihttps://hdl.handle.net/20.500.14352/102744
dc.issue.number8
dc.journal.titleBlood
dc.language.isoeng
dc.page.final2923
dc.page.initial2916
dc.relation.projectIDSAF2005-02228
dc.relation.projectIDCAM 08.4/0023/2003
dc.relation.projectIDGR/SAL/0309/2004
dc.relation.projectIDCP03/00 025
dc.relation.projectIDSAF2005- 06025
dc.relation.projectIDinfo:eu-repo/grantAgreement/MEC//SAF2006-02410/ES/MODELOS EXPERIMENTALES DE FISIOPATOLOGIA VASCULAR : DE LA MODIFICACION POSTRADUCCIONAL AL ANIMAL TRANSGENICO/
dc.relation.projectIDAR47074
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu577.1
dc.subject.cdu577.2
dc.subject.ucmBioquímica (Farmacia)
dc.subject.ucmBiología molecular (Farmacia)
dc.subject.unesco2302 Bioquímica
dc.titleFunctional interplay between endothelial nitric oxide synthase and membrane type 1–matrix metalloproteinase in migrating endothelial cells
dc.typejournal article
dc.type.hasVersionAM
dc.volume.number110
dspace.entity.typePublication
relation.isAuthorOfPublicationeec0b303-34c9-47dd-9ec6-704b6c6c7acd
relation.isAuthorOfPublication.latestForDiscoveryeec0b303-34c9-47dd-9ec6-704b6c6c7acd
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