Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythermatosus

Aleksandar K. Stanic, Charles M. Stein, Adam C. Morgan, Sergio Fazio, MacRae F. Linton, Edward K. Wakeland, Nancy J. Olsen, Amy S. Major

    Research output: Contribution to journalArticle

    57 Scopus citations


    Patients with systemic lupus erythematosus (SLE) have accelerated atherosclerosis. The underlying mechanisms are poorly understood, and investigations have been hampered by the absence of animal models that reflect the human condition of generalized atherosclerosis and lupus. We addressed this problem by transferring lupus susceptibility to low-density lipoprotein (LDL) receptor-deficient (LDLr-/-) mice, an established model of atherosclerosis, creating radiation chimeras with NZM2410-derived, lupus-susceptible, B6.S/e1.2.3 congenic or C57BL/6 control donors (LDLr.S/e and LDLr.B6, respectively). LDLr.S/e mice developed a lupus-like disease characterized by production of double-stranded DNA autoantibodies and renal disease. When fed a Western-type diet, LDLr.S/e chimeras had increased mortality and atherosclerotic lesions. The plaques of LDLr.S/e mice were highly inflammatory and contained more CD3+ T cells than controls. LDLr.S/e mice also had increased activation of CDA+ T and B cells and significantly higher antibody to oxidized LDL and cardiolipin. Collectively, these studies demonstrate that the lupus-susceptible immune system enhances atherogenesis and modulates plaque composition.

    Original languageEnglish (US)
    Pages (from-to)7018-7023
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Issue number18
    StatePublished - May 2 2006


    • Autoimmunity
    • Congenic mice

    ASJC Scopus subject areas

    • General

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