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Journal article

Endothelial nitric oxide synthase gene transfer restores endothelium–dependent relaxations and attenuates lesion formation in carotid arteries in apolipoprotein E–deficient mice

  • Mujynya-Ludunge, Kathi Division of Cardiology, Faculty of Biology and Medicine, University of Lausanne, Switzerland - Institute of Microbiology, Faculty of Biology and Medicine, University of Lausanne, Switzerland
  • Viswambharan, Hema Physiology Unit, Department of Medicine, University of Fribourg, Switzerland
  • Driscoll, Robert Division of Cardiology, Faculty of Biology and Medicine, University of Lausanne, Switzerland
  • Ming, Xiu-Fen Physiology Unit, Department of Medicine, University of Fribourg, Switzerland
  • Segesser, Ludwig K. von Division of Cardiovascular Surgery, Faculty of Biology and Medicine, University of Lausanne, Switzerland
  • Kappenberger, Lukas Division of Cardiology, Faculty of Biology and Medicine, University of Lausanne, Switzerland
  • Yang, Zhihong Physiology Unit, Department of Medicine, University of Fribourg, Switzerland
  • Vassalli, Giuseppe Division of Cardiology, Faculty of Biology and Medicine, University of Lausanne, Switzerland - Institute of Microbiology, Faculty of Biology and Medicine, University of Lausanne, Switzerland
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    24.11.2004
Published in:
  • Basic Research in Cardiology. - 2005, vol. 100(2), p. 102
NO-synthase
MCP–1
arteriosclerosis
endothelium
apolipoprotein–E
mouse
gene therapy
English 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Medicine
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/299992
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