Autoimmune-mediated reduction of high-density lipoprotein-cholesterol and paraoxonase 1 activity in systemic lupus erythematosus-prone gld mice.
Autoimmune-mediated reduction of high-density lipoprotein-cholesterol and paraoxonase 1 activity in systemic lupus erythematosus-prone gld mice.
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DOI：
10.1002/art.27764
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发表时间：
2011-01
影响因子：
--
通讯作者：
Kabarowski, Janusz H.
中科院分区：
文献类型：
--
作者：
Srivastava, Roshni;Yu, Shaohua;Parks, Brian W.;Black, Leland L.;Kabarowski, Janusz H.
描述自身免疫性gld（全身性淋巴组织增生性疾病）小鼠中可能与系统性红斑狼疮过早动脉粥样硬化相关的高密度脂蛋白（HDL）修饰，并评估其与自身免疫性疾病特定方面的关系。在老龄雌性gld和野生型（WT）同源小鼠中测定了HDL-胆固醇（HDL-C）、载脂蛋白-A1（ApoA 1）、对氧磷酶-1（PON 1）活性、肝脏基因表达和HDL生物合成。采用酶联免疫吸附试验、流式细胞术和多重免疫分析法分别检测自身抗体、淋巴器官和细胞因子。血浆HDL-C，HDL-ApoA 1和HDL相关的PON 1活性在老龄gld小鼠中降低，与自身免疫的发展相关，与肝脏ApoA 1和PON 1表达或HDL生物合成的变化无关。肝脏诱导的急性期反应物，血清淀粉样蛋白A-1，导致其纳入高密度脂蛋白在gld小鼠。在gld小鼠（G2 A-/-gld）中删除脂质敏感性受体G2 A可减弱HDL-C和PON 1活性的降低，而不改变肝脏ApoA 1和PON 1表达、HDL生物合成或急性期促炎细胞因子水平。血浆抗ApoA 1自身抗体在老龄gld小鼠中升高，与ApoA 1免疫复合物的可检测增加相称。与gld小鼠相比，老化的G2 A-/-gld小鼠中的自身抗体较低，并且在自身免疫性gld和G2 A-/-gld小鼠中，抗ApoA 1自身抗体水平与HDL-C浓度（r=-0.645，p <0.0004）和PON 1活性（r=-0.555，p<0.0007）显著相关。抗ApoA 1自身抗体有助于降低自身免疫性gld小鼠的HDL-C和PON 1活性，这与肝脏HDL生物合成无关，表明HDL免疫复合物的功能损害和过早清除可能是主要机制。
To characterize modifications of high-density lipoprotein (HDL) in autoimmune gld (generalized lymphoproliferative disorder) mice that may be relevant to premature atherosclerosis in systemic lupus erythematosus and assess their relationship to specific aspects of autoimmune disease. HDL-cholesterol (HDL-C), apolipoprotein-A1 (ApoA1), paraoxonase-1 (PON1) activity, hepatic gene expression and HDL biogenesis were measured in ageing female gld and wild-type (WT) congenic mice. Autoantibodies, lymphoid organs and cytokines were analyzed by enzyme-linked immunosorbent assay, flow cytometry and multiplex assay respectively. Plasma HDL-C, HDL-ApoA1 and HDL-associated PON1 activity were reduced in ageing gld mice in association with the development of autoimmunity independently of changes in hepatic ApoA1 and PON1 expression or HDL biogenesis. Hepatic induction of the acute phase reactant, serum amyloid A-1, resulted in its incorporation onto HDL in gld mice. Deletion of the lipid-sensitive receptor, G2A, in gld mice (G2A-/-gld) attenuated reductions in HDL-C and PON1 activity without altering hepatic ApoA1 and PON1 expression, HDL biogenesis or levels of acute phase pro-inflammatory cytokines. Plasma anti-ApoA1 autoantibodies were elevated in ageing gld mice commensurate with detectable increases in ApoA1 immune complexes. Autoantibodies were lower in ageing G2A-/-gld mice compared to gld mice and anti-ApoA1 autoantibody levels were significantly related to HDL-C concentration (r=-0.645, p<0.00004) and PON1 activity (r=-0.555, p<0.0007) amongst autoimmune gld and G2A-/-gld mice. Autoantibodies against ApoA1 contribute to reducing HDL-C and PON1 activity in autoimmune gld mice independently of hepatic HDL biogenesis, suggesting that functional impairment and premature clearance of HDL immune complexes may be principal mechanisms involved.
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DOI：
10.1161/atvbaha.108.178681
发表时间：
2009-02
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Jahangiri A;de Beer MC;Noffsinger V;Tannock LR;Ramaiah C;Webb NR;van der Westhuyzen DR;de Beer FC
通讯作者：
de Beer FC
影响因子：
6.5
作者：
Feng, Xuebing;Li, Hongyun;Tsao, Betty P.
通讯作者：
Tsao, Betty P.
DOI：
10.1196/annals.1422.016
发表时间：
2007-01-01
期刊：
AUTOIMMUNITY, PT D
影响因子：
--
作者：
Batuca, J. R.;Ames, P. R. J.;Alves, J. Delgado
通讯作者：
Alves, J. Delgado
影响因子：
--
作者：
Cederholm, A;Svenungsson, E;Frosteg책rd, J
通讯作者：
Frosteg책rd, J
功能障碍的促炎高密度脂蛋白赋予了全身性红斑狼疮女性动脉粥样硬化的风险。
影响因子：
--
作者：
McMahon, Maureen;Grossman, Jennifer;Skaggs, Brian;FitzGerald, John;Sahakian, Lori;Ragavendra, Nagesh;Charles-Schoeman, Christina;Watson, Karol;Wong, Weng Kee;Volkmann, Elizabeth;Chen, Weiling;Gorn, Alan;Karpouzas, George;Weisman, Michael;Wallace, Daniel J.;Hahn, Bevra H.
通讯作者：
Hahn, Bevra H.