Genís, LauraGonzalo, PilarTutor, Antonio S.Gálvez, Beatriz G.Martínez Ruiz, AntonioZaragoza, CarlosLamas, SantiagoTryggvason, KarlApte, Suneel S.Arroyo, Alicia G.2024-04-052024-04-052007-10-150006-49711528-002010.1182/blood-2007-01-068080https://hdl.handle.net/20.500.14352/102744Nitric 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationaljournal articlehttps://ashpublications.org/blood/article/110/8/2916/23981/Functional-interplay-between-endothelial-nitricopen access577.1577.2Bioquímica (Farmacia)Biología molecular (Farmacia)2302 Bioquímica