To establish a mouse model of accelerated atherosclerosis in lupus, we generated apolipoprotein E-deficient (apoE-/-) and Fas lpr/lpr (Fas-/-) C57BL/6 mice. On a normal chow diet, 5 month old apoE-/-Fas-/- mice had enlarged glomerular tuft areas, severe proteinuria, increased circulating autoantibody levels, and increased apoptotic cells in renal and vascular lesions compared with either single knockout mice. Also, double knockout mice developed increased atherosclerotic lesions but decreased serum levels of total and non-HDL cholesterol compared with apoE-/-Fas+/+ littermates. Moreover, female apoE-/-Fas-/- mice had lower vertebral bone mineral density (BMD) and bone volume density (BV/TV) than age-matched female apoE-/-Fas-/- mice. Compared with apoE -/-Fas+/+ and apoE+/+Fas-/- mice, apoE-/-Fas-/- mice had decreased circulating oxidized phospholipid (OxPL) content on apoB-100 containing lipoprotein particles and increased serum IgG antibodies to OxPL, which were significantly correlated with aortic lesion areas (r = 0.58), glomerular tuft areas (r = 0.87), BMD (r = -0.57), and BV/TV (r = -0.72). These results suggest that the apoE -/-Fas-/- mouse model might be used to study atherosclerosis and osteopenia in lupus. Correlations of IgG anti-OxPL with lupus-like disease, atherosclerosis, and bone loss suggested a shared pathway of these disease processes. Copyright ©2007 by the American Society for Biochemistry and Molecular Biology, Inc.

ApoE-/-Fas-/- C57BL/6 mice: A novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia / Feng, X.; Li, H.; Rumbin, A. A.; Wang, X.; La Cava, A.; Brechtelsbauer, K.; Castellani, L. W.; Witztum, J. L.; Lusis, A. J.; Tsao, B. P.. - In: JOURNAL OF LIPID RESEARCH. - ISSN 0022-2275. - 48:4(2007), pp. 794-805. [10.1194/jlr.M600512-JLR200]

ApoE-/-Fas-/- C57BL/6 mice: A novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia

La Cava A.;
2007

Abstract

To establish a mouse model of accelerated atherosclerosis in lupus, we generated apolipoprotein E-deficient (apoE-/-) and Fas lpr/lpr (Fas-/-) C57BL/6 mice. On a normal chow diet, 5 month old apoE-/-Fas-/- mice had enlarged glomerular tuft areas, severe proteinuria, increased circulating autoantibody levels, and increased apoptotic cells in renal and vascular lesions compared with either single knockout mice. Also, double knockout mice developed increased atherosclerotic lesions but decreased serum levels of total and non-HDL cholesterol compared with apoE-/-Fas+/+ littermates. Moreover, female apoE-/-Fas-/- mice had lower vertebral bone mineral density (BMD) and bone volume density (BV/TV) than age-matched female apoE-/-Fas-/- mice. Compared with apoE -/-Fas+/+ and apoE+/+Fas-/- mice, apoE-/-Fas-/- mice had decreased circulating oxidized phospholipid (OxPL) content on apoB-100 containing lipoprotein particles and increased serum IgG antibodies to OxPL, which were significantly correlated with aortic lesion areas (r = 0.58), glomerular tuft areas (r = 0.87), BMD (r = -0.57), and BV/TV (r = -0.72). These results suggest that the apoE -/-Fas-/- mouse model might be used to study atherosclerosis and osteopenia in lupus. Correlations of IgG anti-OxPL with lupus-like disease, atherosclerosis, and bone loss suggested a shared pathway of these disease processes. Copyright ©2007 by the American Society for Biochemistry and Molecular Biology, Inc.
2007
ApoE-/-Fas-/- C57BL/6 mice: A novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia / Feng, X.; Li, H.; Rumbin, A. A.; Wang, X.; La Cava, A.; Brechtelsbauer, K.; Castellani, L. W.; Witztum, J. L.; Lusis, A. J.; Tsao, B. P.. - In: JOURNAL OF LIPID RESEARCH. - ISSN 0022-2275. - 48:4(2007), pp. 794-805. [10.1194/jlr.M600512-JLR200]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/885922
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