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Endothelial nitric oxide synthase genetransfer restores endothelium-dependentrelaxations and attenuates lesion formationin carotid arteries in apolipoproteinE-deficient mice

Mujynya-Ludunge, Kathi ; Viswambharan, Hema ; Driscoll, Robert ; Ming, Xiu-Fen ; von Segesser, Ludwig ; Kappenberger, Lukas ; Yang, Zhihong ; Vassalli, Giuseppe

In: Basic Research in Cardiology, 2005, vol. 100, no. 2, p. 102-111

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    Titre
    • Endothelial nitric oxide synthase genetransfer restores endothelium-dependentrelaxations and attenuates lesion formationin carotid arteries in apolipoproteinE-deficient mice
    Auteur
    • Mujynya-Ludunge, Kathi. Division of Cardiology, University of Lausanne, Faculty of Biology and Medicine CHUV-BH10, 1011, Lausanne, Switzerland
    • Viswambharan, Hema. Institute of Physiology, University of Fribourg, Fribourg, Switzerland
    • Driscoll, Robert. Division of Cardiology, University of Lausanne, Faculty of Biology and Medicine CHUV-BH10, 1011, Lausanne, Switzerland
    • Ming, Xiu-Fen. Institute of Physiology, University of Fribourg, Fribourg, Switzerland
    • von Segesser, Ludwig. Division of Cardiovascular Surgery, University of Lausanne Faculty of Biology and Medicine, Lausanne, Switzerland
    • Kappenberger, Lukas. Division of Cardiology, University of Lausanne, Faculty of Biology and Medicine CHUV-BH10, 1011, Lausanne, Switzerland
    • Yang, Zhihong. Institute of Physiology, University of Fribourg, Fribourg, Switzerland
    • Vassalli, Giuseppe. Division of Cardiology, University of Lausanne, Faculty of Biology and Medicine CHUV-BH10, 1011, Lausanne, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Basic Research in Cardiology, 2005, vol. 100, no. 2, p. 102-111. Steinkopff-Verlag
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:310020
    Summary
    Nitric oxide (NO) and monocyte chemoattractant protein-1 (MCP-1) exert partly opposing effects in vascular biology. NO plays pleiotropic vasoprotective roles including vasodilation and inhibition of platelet aggregation, smooth muscle cell proliferation, and endothelial monocyte adhesion, the last effect being mediated by MCP-1 downregulation. Early stages of arteriosclerosis are associated with reduced NO bioactivity and enhanced MCP-1 expression. We have evaluated adenovirus-mediated gene transfer of human endothelial NO synthase (eNOS) and of a N-terminal deletion (8ND) mutant of the MCP-1 gene that acts as a MCP-1 inhibitor in arteriosclerosis-prone, apolipoprotein E-deficient (ApoE-/-) mice. Endotheliumdependent relaxations were impaired in carotid arteries instilled with a noncoding adenoviral vector but were restored by eNOS gene transfer (p < 0.01). A perivascular collar was placed around the common carotid artery to accelerate lesion formation. eNOS gene transfer reduced lesion surface areas, intima/media ratios, and macrophage contents in the media at 5-week follow-up (p < 0.05). In contrast, 8ND-MCP-1 gene transfer did not prevent lesion formation. In conclusion, eNOS gene transfer restores endothelium-dependent vasodilation and inhibits lesion formation in ApoE-/- mouse carotids. Further studies are needed to assess whether vasoprotection is maintained at later disease stages and to evaluate the long-term efficacy of eNOS gene therapy for primary arteriosclerosis