β2-glycoprotein I gene deficiency (β2GPI-Sapporo) and the progression of atherosclerosis
β2-glycoprotein I gene deficiency (β2GPI-Sapporo) and the progression of atherosclerosis
批准号:
12557043
负责人:
KOIKE Takao
金额:
$8.38万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2000
资助国家:
日本
项目状态:
已结题
起止时间:
2000 至 2002
中文摘要
最近的证据表明,抗磷脂抗体可能有助于动脉粥样硬化病变的形成。在小于45岁的SLE中,心肌梗死已被认为是死亡的主要原因。作者曾报道抗磷脂综合征(APS)患者的aCL并不简单地与CL结构有关,而是需要β2-糖蛋白I(β 2-GPI)的存在才能结合,并且当β 2-GPI与氧取代的固体表面相互作用时,其表位通过构象变化而表达。β 2GPI与氧化型LDL和氧化型脂蛋白特异性结合,尤其是氧化型LDL,也是β2GPI和aCL的相继靶点,这种免疫反应不仅参与血浆脂蛋白的代谢,而且参与APS中血栓性并发症伴动脉粥样硬化事件的发生。发现2个β2GPI完全缺乏症家系。β2GPI基因缺失的个体,其β 2GPI基因cDNA第379位的胸腺嘧啶缺失。在日本人中,这种杂合子缺陷的发生率为6.3%,而在高加索人中,杂合子的血清β2GPI浓度与无突变者相比显著降低,但未观察到显著不同的脂质谱,如总胆固醇、甘油三酯、HDL-胆固醇、LDL-胆固醇、apoA-I、apoB和Lp(a)。低浓度的β2GPI似乎与脂蛋白代谢的明显异常无关。
英文摘要
Recent evidence suggested that antiphospholipid antibodies may have contributed to the formation of atherosclerotic lesions. In SLE less than 45 years of age, myocardial infarction has been recognized as a major cause of mortality. I have reported that aCL found in patients with antiphospholipid syndrome (APS) are not simply directed to the CL structure, but require the presence of β2-glycoprotein I (β2GPI) for bindng and that the epitopes is expressed by conformational changes occurring whenβ2GPI interacts with an oxygen-substituted solid surface. Β2GPI specifically bound to oxidized LDL and oxidized lipoproteins in the blood, especially oxidized LDL, are also sequentially targeted by β2GPI and aCL, and that immunoreaction is involved not only in the metabolism of plasma lipoproteins but also in thrombotic complications accompanied by atherosclerotic events in APS.Serumβ2GPI concentration of 812 apparently healthy Japanese individuals was measured by sandwich EIA. Two families with completeβ2GPI deficiency were identified. A thymine corresponding to position 379 of the β2GPI cDNA was deleted in every β2GPI deficient individual. The incidence of this heterozygous deficiency determined by RFLP was 6.3% in Japanese and none in Caucasians Heterozygotes had significantly lower concentrations of serumβ2GPI than did those without the mutation, yet no significantly different lipid profiles, such as total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apoA-I, apoB and Lp(a), were observed. A low concentration ofβ2GPI seemed not to be associated with apparent abnormality in lipoprotein metabolism.
期刊论文(70)
专著(0)
科研奖励(0)
会议论文
登录
查看更多内容
Bertlaccini, M.L.: "Plasma tumor necrosis factor a levels and the -238^* a promoter polymorphism in patients with antiphospholipid syndrome"Thromb Haemost. 85. 198-203 (2001)
Bertlaccini, M.L.:“抗磷脂综合征患者的血浆肿瘤坏死因子 a 水平和 -238^* a 启动子多态性”Thromb Haemost。
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
小池 隆夫, 他221名: "内科学"朝倉書店. 2297 (2003)
Takao Koike 等 221:《内科》朝仓书店 2297 (2003)。
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
Tincani, A., Allegri, F., Sanmarco, M., Cinquini, M., Taglieti, M., Balestrieri, G., Koike, T., Ichikawa, K., Meroni, P., Boffa, M.C.: "Antidardiolipin antibody assey : a methodological analysis for a better consensus in routine depterminations"Thromb Hae
Tincani, A.、Allegri, F.、Sanmarco, M.、Cinquini, M.、Tagliet, M.、Balestrieri, G.、Koike, T.、Ichikawa, K.、Meroni, P.、Boffa, M.C.:“
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
Horita, T., Tsutsumi, A., Takeda, T., Yasuda, S., Takeuti, R., Amasaki, Y., Ichikawa, K., Atsumi, T., Koike, T: "Significance of magnetic resonace imafing in diagnosis of nodular regenerative hyperplasia of the liver complicated with systemic lupus erythe
Horita, T.、Ttsutsumi, A.、Takeda, T.、Yasuda, S.、Takeuti, R.、Amasaki, Y.、Ichikawa, K.、Atsumi, T.、Koike, T:“磁共振成像的意义
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
Atsumi, T., Koike, T.: "Clinical relevance of antiprothrombin antibodies"Autoimmunity Reviews. 1. 49-53 (2002)
Atsumi,T.,Koike,T.:“抗凝血酶原抗体的临床相关性”自身免疫评论。
DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
共 34 条
The analysis of molecular pathogenesis and mechanisms for antiphospholipid syndrome
-
批准号:22390198
-
项目类别:Grant-in-Aid for Scientific Research (B)
-
资助金额:$11.98万
-
财政年份:2010
-
负责人:KOIKE Takao
-
依托单位:
Rural Homelessness in Japan with a special focus on the Tohoku Region
-
批准号:19730357
-
项目类别:Grant-in-Aid for Young Scientists (B)
-
资助金额:$1.57万
-
财政年份:2007
-
负责人:KOIKE Takao
-
依托单位:
Pathogenesis of antiphospholipid syndrome and new therapeutic target
-
批准号:19390269
-
项目类别:Grant-in-Aid for Scientific Research (B)
-
资助金额:$11.98万
-
财政年份:2007
-
负责人:KOIKE Takao
-
依托单位:
Pathogenesis of antiphospholipid antibodies:
-
批准号:17390286
-
项目类别:Grant-in-Aid for Scientific Research (B)
-
资助金额:$9.79万
-
财政年份:2005
-
负责人:KOIKE Takao
-
依托单位:
The p38 mitogen-activated protein kinasa (MAPK) pathway mediates induction of the tissue factor gene in monocytes stimulated with human monoclonal anti β2Glycoprotein I antibodies
-
批准号:15390310
-
项目类别:Grant-in-Aid for Scientific Research (B)
-
资助金额:$7.81万
-
财政年份:2003
-
负责人:KOIKE Takao
-
依托单位:
β2-glycoprotein I gene polymorphism ; Risk factor for the development of antiphospholipid syndrome.
-
批准号:13470105
-
项目类别:Grant-in-Aid for Scientific Research (B)
-
资助金额:$9.22万
-
财政年份:2001
-
负责人:KOIKE Takao
-
依托单位:
Anticardiolipin Antibodies and Obstructive Vascular Events
-
批准号:11470122
-
项目类别:Grant-in-Aid for Scientific Research (B).
-
资助金额:$9.09万
-
财政年份:1999
-
负责人:KOIKE Takao
-
依托单位:
Analysis of thrombosis formation in patients with antiphospholipid syndrome
-
批准号:08457150
-
项目类别:Grant-in-Aid for Scientific Research (B)
-
资助金额:$1.28万
-
财政年份:1996
-
负责人:KOIKE Takao
-
依托单位:
Establishment of a novel assay method for anticardiolipin antibodies.
-
批准号:07557221
-
项目类别:Grant-in-Aid for Scientific Research (B)
-
资助金额:$0.9万
-
财政年份:1995
-
负责人:KOIKE Takao
-
依托单位:
Anticardiolipin antibody and the development of arterial and venous thrombosis.
-
批准号:06454249
-
项目类别:Grant-in-Aid for General Scientific Research (B)
-
资助金额:$4.54万
-
财政年份:1994
-
负责人:KOIKE Takao
-
依托单位:
The role of anticardiolipin antibodies on the development of thromboembolic manifestations in patients with collagen autoimmune disorders
-
批准号:04670370
-
项目类别:Grant-in-Aid for General Scientific Research (C)
-
资助金额:$1.34万
-
财政年份:1992
-
负责人:KOIKE Takao
-
依托单位:
Activation and differentiation of eosinophils in asthma
-
批准号:01480234
-
项目类别:Grant-in-Aid for General Scientific Research (B)
-
资助金额:$4.1万
-
财政年份:1989
-
负责人:KOIKE Takao
-
依托单位:
Role of anti-DNA antibody and anti-cardiolipin antibody for the progression of vasculopathy in collagen diseases
-
批准号:01570348
-
项目类别:Grant-in-Aid for General Scientific Research (C)
-
资助金额:$1.34万
-
财政年份:1989
-
负责人:KOIKE Takao
-
依托单位:
Pathological Significance of Anti-DNA Antibodies: analysis using monoclonal antibodies
-
批准号:62570277
-
项目类别:Grant-in-Aid for General Scientific Research (C)
-
资助金额:$1.34万
-
财政年份:1987
-
负责人:KOIKE Takao
-
依托单位:
Analysis of autoantibody production and regulation system using monoclonal anti-DNA antibodies
-
批准号:60570285
-
项目类别:Grant-in-Aid for General Scientific Research (C)
-
资助金额:$1.09万
-
财政年份:1985
-
负责人:KOIKE Takao
-
依托单位: