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Transgenic human CRP is not pro-atherogenic, pro-atherothrombotic or pro-inflammatory in apoE−/− mice

  • Author Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Glenys A. Tennent
    Correspondence
    Corresponding author at: Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine (Hampstead Campus), Royal Free & University College Medical School, Rowland Hill St, London NW3 2PF, UK. Tel.: +44 20 433 2806; fax: +44 20 7433 2817.
    Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Affiliations
    Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK
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  • Author Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Winston L. Hutchinson
    Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Affiliations
    Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK
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  • Author Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Melvyn C. Kahan
    Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Affiliations
    Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK
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  • Author Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Gideon M. Hirschfield
    Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Affiliations
    Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK
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  • Author Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    J. Ruth Gallimore
    Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Affiliations
    Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK
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  • Author Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Jackie Lewin
    Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Affiliations
    Electron Microscopy Unit, University College London, UK
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  • Author Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Caroline A. Sabin
    Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Affiliations
    Department of Primary Care and Population Sciences, University College London, UK
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  • Author Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Amar P. Dhillon
    Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Affiliations
    Department of Histopathology, University College London, UK
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  • Author Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Mark B. Pepys
    Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
    Affiliations
    Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK
    Search for articles by this author
  • Author Footnotes
    1 All investigators are from the Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.

      Abstract

      The pathogenic significance, if any, of the epidemiological association between baseline C-reactive protein (CRP) values and future atherothrombotic events is not known. We therefore investigated spontaneous atherosclerosis and atherothrombosis, and systemic markers of inflammation (acute phase proteins), in aged, normal diet-fed, male apolipoprotein E deficient (apoE−/−) mice with and without transgenic expression of human CRP. At 18 months of age, aortic atherosclerosis was extensive but with no significant difference in plaque size between C57BL/6apoE−/− mice with (apoE−/−-hCRP+) and without transgenic human CRP (apoE−/−). Atherosclerotic lesions in brachiocephalic arteries were typically complex and layered, with extensive fibrotic-cholesterol deposits, calcification and occasional recent intraplaque haemorrhage and thrombus, but with no significant overall differences between apoE−/− and apoE−/−-hCRP+ animals. Concentrations of mouse serum amyloid P component (SAP) were essentially normal throughout and did not differ between apoE−/− and apoE−/−-hCRP+ mice, or between wild-type (apoE+/+) and apoE−/− mice, regardless of human CRP expression. Mouse serum amyloid A protein (SAA), and human CRP concentrations were modestly but significantly higher in apoE−/−-hCRP+ than in apoE+/+-hCRP+ animals, but mouse SAA values were unaffected by transgenic expression of human CRP in either background. Thus, there was no evidence in this 18 month study of apoE−/−, and control apoE+/+ mice, that transgenic human CRP was pro-atherogenic, pro-inflammatory or pro-atherothrombotic.

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