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Publication
Immune dysregulation accelerates atherosclerosis and modulates plaque
composition in systemic lupus erythematosus.
Authors Stanic AK, Stein CM, Morgan AC, Fazio S, Linton MF, Wakeland EK, Olsen NJ, Major
AS
Submitted By Amy Major on 11/12/2007
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2006
Date Published 5/2/2006
Volume : Pages 103 : 7018 - 7023
PubMed Reference 16636270
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.Sle1.2.3
congenic or C57BL/6 control donors (LDLr.Sle and LDLr.B6, respectively).
LDLr.Sle mice developed a lupus-like disease characterized by production of
double-stranded DNA autoantibodies and renal disease. When fed a Western-type
diet, LDLr.Sle chimeras had increased mortality and atherosclerotic lesions. The
plaques of LDLr.Sle mice were highly inflammatory and contained more CD3+ T
cells than controls. LDLr.Sle mice also had increased activation of CD4+ 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.






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