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Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery

Tanner, F. ; van der Loo, B. ; Shaw, S. ; Greutert, H. ; Bachschmid, M. ; Berrozpe, M. ; Rozenberg, I. ; Blau, N. ; Siebenmann, R. ; Schmidli, J. ; Meyer, P. ; Lüscher, T.

In: Basic Research in Cardiology, 2007, vol. 102, no. 4, p. 308-317

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    Titre
    • Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery
    Auteur
    • Tanner, F.. Cardiovascular Research, Physiology Institute University of Zürich, Zürich, Switzerland
    • van der Loo, B.. Cardiovascular Research, Physiology Institute University of Zürich, Zürich, Switzerland
    • Shaw, S.. Dept. of Clinical Research, University Hospital, Bern, Switzerland
    • Greutert, H.. Cardiovascular Research, Physiology Institute University of Zürich, Zürich, Switzerland
    • Bachschmid, M.. Dept. of Biology, University of Konstanz, Konstanz, Germany
    • Berrozpe, M.. Cardiovascular Research, Physiology Institute University of Zürich, Zürich, Switzerland
    • Rozenberg, I.. Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland
    • Blau, N.. Clinical Chemistry, University Children's Hospital, Zürich, Switzerland
    • Siebenmann, R.. Cardiovascular Surgery, Herzzentrum Hirslanden, Zürich, Switzerland
    • Schmidli, J.. Cardiovascular Surgery, University Hospital, Bern, Switzerland
    • Meyer, P.. Ophthalmology, University Hospital, Basel, Switzerland
    • Lüscher, T.. Cardiovascular Research, Physiology Institute University of Zürich, Zürich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Basic Research in Cardiology, 2007, vol. 102, no. 4, p. 308-317. Steinkopff-Verlag
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:310401
    Summary
    Objective : Nitric oxide (NO) inhibits thrombus formation, vascular contraction, and smooth muscle cell proliferation. We investigated whether NO release is enhanced after endothelial NO synthase (eNOS) gene transfer in atherosclerotic human carotid artery ex vivo. Methods and Results : Western blotting and immunohistochemistry revealed that transduction enhanced eNOS expression; however, neither nitrite production nor NO release measured by porphyrinic microsensor was altered. In contrast, transduction enhanced NO production in non-atherosclerotic rat aorta and human internal mammary artery. In transduced carotid artery, calcium-dependent eNOS activity was minimal and did not differ from control conditions. Vascular tetrahydrobiopterin concentrations did not differ between the experimental groups.Treatment of transduced carotid artery with FAD, FMN, NADPH, L-arginine, and either sepiapterin or tetrahydrobiopterin did not alter NO release. Superoxide formation was similar in transduced carotid artery and control. Treatment of transduced carotid artery with superoxide dismutase (SOD), PEG-SOD, PEG-catalase did not affect NO release. Conclusions : eNOS transduction in atherosclerotic human carotid artery results in high expression without any measurable activity of the recombinant protein. The defect in the atherosclerotic vessels is neither caused by cofactor deficiency nor enhanced NO breakdown. Since angioplasty is performed in atherosclerotic arteries,eNOS gene therapy is unlikely to provide clinical benefit