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

56 Citations (Scopus)

Abstract

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
Volume103
Issue number18
DOIs
StatePublished - May 2 2006

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Atherosclerosis
Radiation Chimera
T-Lymphocytes
Cardiolipins
LDL Receptors
Systemic Lupus Erythematosus
Autoantibodies
Immune System
B-Lymphocytes
Animal Models
Tissue Donors
Kidney
Mortality
Antibodies
DNA

Keywords

  • Autoimmunity
  • Congenic mice

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythermatosus. / Stanic, Aleksandar K.; Stein, Charles M.; Morgan, Adam C.; Fazio, Sergio; Linton, MacRae F.; Wakeland, Edward K.; Olsen, Nancy J.; Major, Amy S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 18, 02.05.2006, p. 7018-7023.

Research output: Contribution to journalArticle

Stanic, Aleksandar K. ; Stein, Charles M. ; Morgan, Adam C. ; Fazio, Sergio ; Linton, MacRae F. ; Wakeland, Edward K. ; Olsen, Nancy J. ; Major, Amy S. / Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythermatosus. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 18. pp. 7018-7023.
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