2026-06-14T03:33:08Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/273512026-03-26T01:23:02Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587
Repisalud
author
Genís, Laura
author
Gonzalo, Pilar
author
Tutor, Antonio S
author
Gálvez, Beatriz G
author
Martínez-Ruiz, Antonio
author
Zaragoza, Carlos
author
Lamas, Santiago
author
Tryggvason, Karl
author
Apte, Suneel S
author
Arroyo, Alicia G
2026-03-25T15:49:37Z
2026-03-25T15:49:37Z
2007-10-15
Blood. 2007 Oct 15;110(8):2916-23.
Blood
17606763
https://hdl.handle.net/20.500.12105/27351
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 motility-associated 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 NO-induced 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
Functional interplay between endothelial nitric oxide synthase and membrane type 1 matrix metalloproteinase in migrating endothelial cells.
research article
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URL
https://repisalud.isciii.es/bitstreams/c7c3266c-b27d-456e-89e9-c6d311d528c4/download
File
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538296d8a89c644ac1d13eb15ab89f7b
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application/pdf
Functional interplay between endothelial nitric oxide_Blood_2007.pdf