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

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. 2024-04-05T11:05:16Z 2024-04-05T11:05:16Z 2007-10-15 0006-4971 1528-0020 10.1182/blood-2007-01-068080 https://hdl.handle.net/20.500.14352/102744 https://ashpublications.org/blood/article/110/8/2916/23981/Functional-interplay-between-endothelial-nitric 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. eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 International Functional interplay between endothelial nitric oxide synthase and membrane type 1–matrix metalloproteinase in migrating endothelial cells journal article