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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2916-2923. Prepublished online as a Blood First Edition Paper on July 2, 2007; DOI 10.1182/blood-2007-01-068080. This Article Full Text Full Text (PDF) Supplemental Figures and Video All Versions of this Article: blood-2007-01-068080v1 110/8/2916    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Genís, L. Articles by Arroyo, A. G. Search for Related Content PubMed PubMed Citation Articles by Genís, L. Articles by Arroyo, A. G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Functional interplay between endothelial nitric oxide synthase and membrane type 1–matrix metalloproteinase in migrating endothelial cells Laura Genís1, Pilar Gonzalo1, Antonio S. Tutor1, Beatriz G. Gálvez1, Antonio Martínez-Ruiz1, Carlos Zaragoza1, Santiago Lamas2, Karl Tryggvason3, Suneel S. Apte4, and Alicia G. Arroyo1 1 Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; 2 Centro de Investigaciones Biológicas, Instituto "Reina Sofia" de Investigaciones Nefrológicas (CSIC), Madrid, Spain; 3 Matrix Biology and Biochemistry, Karolinska Institute, Stockholm, Sweden; 4 Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, OH 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Need MT1-MMP? Just say NO! Joseph A. Madri Blood 2007 110: 2790-2791. [Full Text] [PDF] This article has been cited by other articles: K. Sugimoto, T. Ishibashi, T. Sawamura, N. Inoue, M. Kamioka, H. Uekita, H. Ohkawara, T. Sakamoto, N. Sakamoto, Y. Okamoto, et al. LOX-1-MT1-MMP axis is crucial for RhoA and Rac1 activation induced by oxidized low-density lipoprotein in endothelial cells Cardiovasc Res, October 1, 2009; 84(1): 127 - 136. [Abstract] [Full Text] [PDF] A. Alfranca, J. M. Lopez-Oliva, L. Genis, D. Lopez-Maderuelo, I. Mirones, D. Salvado, A. J. Quesada, A. G. Arroyo, and J. M. Redondo PGE2 induces angiogenesis via MT1-MMP-mediated activation of the TGF{beta}/Alk5 signaling pathway Blood, August 15, 2008; 112(4): 1120 - 1128. [Abstract] [Full Text] [PDF] V. W.M. van Hinsbergh and P. Koolwijk Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead Cardiovasc Res, May 1, 2008; 78(2): 203 - 212. [Abstract] [Full Text] [PDF]

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