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

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Abstract

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.

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Authors and Affiliations

  1. Cardiovascular Research, Physiology Institute University of Zürich, Zürich, Switzerland

    F. C. Tanner MD, B. van der Loo MD, H. Greutert, M. Berrozpe PhD & T. F. Lüscher MD

  2. Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland

    F. C. Tanner MD, I. Rozenberg & T. F. Lüscher MD

  3. Dept. of Clinical Research, University Hospital, Bern, Switzerland

    S. Shaw PhD

  4. Dept. of Biology, University of Konstanz, Konstanz, Germany

    M. M. Bachschmid PhD

  5. Clinical Chemistry, University Children’s Hospital, Zürich, Switzerland

    N. Blau PhD

  6. Cardiovascular Surgery, Herzzentrum Hirslanden, Zürich, Switzerland

    R. Siebenmann MD

  7. Cardiovascular Surgery, University Hospital, Bern, Switzerland

    J. Schmidli MD

  8. Ophthalmology, University Hospital, Basel, Switzerland

    P. Meyer MD

  9. Cardiology, Cardiovascular Center, University Hospital, Rämistraße 100, 8091, Zürich, Switzerland

    F. C. Tanner MD, B. van der Loo MD & T. F. Lüscher MD

Authors
  1. F. C. Tanner MD
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  2. B. van der Loo MD
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  3. S. Shaw PhD
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  4. H. Greutert
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  7. I. Rozenberg
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  9. R. Siebenmann MD
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  10. J. Schmidli MD
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  11. P. Meyer MD
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  12. T. F. Lüscher MD
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Corresponding author

Correspondence to T. F. Lüscher MD.

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Tanner, F.C., van der Loo, B., Shaw, S. et al. Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery. Basic Res Cardiol 102, 308–317 (2007). https://doi.org/10.1007/s00395-007-0650-7

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  • DOI: https://doi.org/10.1007/s00395-007-0650-7

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