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Low dose apolipoprotein A-I rescues carotid arteries from inflammation in vivo

  • Rajesh Puranik
    Affiliations
    The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia

    Department of Medicine, University of Sydney, Australia
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  • Shisan Bao
    Affiliations
    The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia

    Department of Pathology, University of Sydney, Australia
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  • Author Footnotes
    1 Current address: INSERM U551, Paris, France.
    Estelle Nobecourt
    Footnotes
    1 Current address: INSERM U551, Paris, France.
    Affiliations
    The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia
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  • Author Footnotes
    2 Current address: Department of Cardiovascular Medicine, Cleveland Clinic Foundation, USA.
    Stephen J. Nicholls
    Footnotes
    2 Current address: Department of Cardiovascular Medicine, Cleveland Clinic Foundation, USA.
    Affiliations
    The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia
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  • Gregory J. Dusting
    Affiliations
    Bernard O’Brien Institute of Microsurgery, University of Melbourne, Melbourne, Australia
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  • Philip J. Barter
    Affiliations
    The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia

    Department of Medicine, University of Sydney, Australia
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  • David S. Celermajer
    Affiliations
    The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia

    Department of Medicine, University of Sydney, Australia
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  • Kerry-Anne Rye
    Correspondence
    Corresponding author. Tel.: +61 2 8208 8900; fax: +61 2 9565 5584.
    Affiliations
    The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia

    Department of Medicine, University of Sydney, Australia

    Department of Medicine, University of Melbourne, Australia
    Search for articles by this author
  • Author Footnotes
    1 Current address: INSERM U551, Paris, France.
    2 Current address: Department of Cardiovascular Medicine, Cleveland Clinic Foundation, USA.

      Abstract

      This study investigates the ability of a single, low dose of apolipoprotein (apo) A-I, the main lipoprotein of high density lipoproteins (HDL), to inhibit acute vascular inflammation in normocholesterolemic New Zealand White rabbits. Acute vascular inflammation was induced in the animals by placing a non-occlusive, silastic collar around the left common carotid artery. The animals (n = 5/group) received a single, low dose infusion of saline or lipid-free apoA-I at the time of, or 3 or 9 h after collar insertion. The animals were sacrificed 24 h post-collar insertion. Inflammatory markers in the artery wall were quantitated immunohistochemically. The saline-treated animals exhibited substantial pan-arterial inflammation, which was inhibited by a single apoA-I infusion (2 or 8 mg/kg) at the time of collar insertion. A single 8 mg/kg infusion of lipid-free apoA-I administered 3 h post-collar insertion reduced neutrophil recruitment into the vessel wall, and MPO expression, as well as endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by >85% (p < 0.01 for all). A single 8 mg/kg infusion of lipid-free apoA-I administered 9 h after collar insertion decreased VCAM-1 expression, neutrophil infiltration and MPO expression by 88% (p < 0.001), 47% (p < 0.01), and 90% (p < 0.01), respectively. This indicates that a single low dose infusion of apoA-I administered after the onset of acute inflammation in carotid arteries decreases neutrophil infiltration and inhibits neutrophil and endothelial cell activation. These findings have potential implications for treating acute vascular inflammation in conditions such as acute coronary and stroke syndromes.

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