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oai:docta.ucm.es:20.500.14352/1027442024-04-05T23:56:48Zcom_20.500.14352_14col_20.500.14352_15

Functional interplay between endothelial nitric oxide synthase and membrane type 1–matrix metalloproteinase in migrating endothelial cells Genís, Laura Gonzalo, Pilar Tutor, Antonio S. Gálvez, Beatriz G. Martínez Ruiz, Antonio Zaragoza, Carlos Lamas, Santiago Tryggvason, Karl Apte, Suneel S. Arroyo, Alicia G. 577.1 577.2 Bioquímica (Farmacia) Biología molecular (Farmacia) 2302 Bioquímica Nitric 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. National Institutes of Health Comunidad Autónoma de Madrid Ministerio de Sanidad y Consumo Ministerio de Educación y Ciencia Depto. de Bioquímica y Biología Molecular Fac. de Farmacia TRUE pub 2024-04-05T11:05:16Z 2024-04-05T11:05:16Z 2007-10-15 journal article AM https://hdl.handle.net/20.500.14352/102744 0006-4971 1528-0020 10.1182/blood-2007-01-068080 eng SAF2005-02228 CAM 08.4/0023/2003 GR/SAL/0309/2004 CP03/00 025 SAF2005- 06025 info:eu-repo/grantAgreement/MEC//SAF2006-02410/ES/MODELOS EXPERIMENTALES DE FISIOPATOLOGIA VASCULAR : DE LA MODIFICACION POSTRADUCCIONAL AL ANIMAL TRANSGENICO/ AR47074 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ open access application/pdf