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Publication : Impaired clearance of apoptotic cells promotes synergy between atherogenesis and autoimmune disease.

First Author  Aprahamian T Year  2004
Journal  J Exp Med Volume  199
Issue  8 Pages  1121-31
PubMed ID  15096538 Mgi Jnum  J:91058
Mgi Id  MGI:3045839 Doi  10.1084/jem.20031557
Citation  Aprahamian T, et al. (2004) Impaired Clearance of Apoptotic Cells Promotes Synergy between Atherogenesis and Autoimmune Disease. J Exp Med 199(8):1121-31
abstractText  To clarify the link between autoimmune disease and hypercholesterolemia, we created the gld.apoE(-/-) mouse as a model of accelerated atherosclerosis. Atherosclerotic lesion area was significantly increased in gld.apoE(-/-) mice compared with apoE(-/-) mice. gld.apoE(-/-) mice also displayed increases in lymphadenopathy, splenomegaly, and autoantibodies compared with gld mice, and these effects were exacerbated by high cholesterol diet. gld.apoE(-/-) mice exhibited higher levels of apoptotic cells, yet a reduced frequency of engulfed apoptotic nuclei within macrophages. Infusion of lysophosphatidylcholine, a component of oxidized low density lipoprotein, markedly decreased apoptotic cell clearance in gld mice, indicating that hypercholesterolemia promotes autoimmune disease in this background. These data suggest that defects in apoptotic cell clearance promote synergy between atherosclerotic and autoimmune diseases.
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