出版社：American Society for Biochemistry and Molecular Biology
摘要：To establish a mouse model of accelerated atherosclerosis inlupus, we generated apolipoprotein E-deficient (apoE–/–)and Faslpr/lpr (Fas–/–) C57BL/6 mice. On a normalchow diet, 5 month old apoE–/–Fas–/–mice had enlarged glomerular tuft areas, severe proteinuria,increased circulating autoantibody levels, and increased apoptoticcells in renal and vascular lesions compared with either singleknockout mice. Also, double knockout mice developed increasedatherosclerotic lesions but decreased serum levels of totaland non-HDL cholesterol compared with apoE–/–Fas+/+littermates. Moreover, female apoE–/–Fas–/–mice had lower vertebral bone mineral density (BMD) and bonevolume density (BV/TV) than age-matched female apoE–/–Fas+/+mice. Compared with apoE–/–Fas+/+ and apoE+/+Fas–/–mice, apoE–/–Fas–/– mice had decreasedcirculating oxidized phospholipid (OxPL) content on apoB-100containing lipoprotein particles and increased serum IgG antibodiesto OxPL, which were significantly correlated with aortic lesionareas (r = 0.58), glomerular tuft areas (r = 0.87), BMD (r =–0.57), and BV/TV (r = –0.72). These results suggestthat the apoE–/–Fas–/– mouse model mightbe used to study atherosclerosis and osteopenia in lupus. Correlationsof IgG anti-OxPL with lupus-like disease, atherosclerosis, andbone loss suggested a shared pathway of these disease processes.Supplementary key words oxidized phospholipid • apoptosis • autoantibodies
Abbreviations: apoE, apolipoprotein E; B6, C57BL/6; BMD, bone mineral density; BV/TV, bone volume density; dsDNA, double-stranded DNA; OxLDL, oxidized low-density lipoprotein; OxPL, oxidized phospholipid; PGPC, 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine; POVPC, 1-palmitoyl-2(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; RLU, relative light units; SLE, systemic lupus erythematosus; TUNEL, TdT-mediated dUTP-biotin nick end labeling
