Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension

Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension
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DOI:
10.1016/j.atherosclerosis.2005.10.017
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发表时间:
2006-09-01
期刊:
影响因子:
5.3
通讯作者:
Frostegard, Johan
Frostegard, Johan
中科院分区:
医学2区
文献类型:
--
作者:
Su, Jun;Georgiades, Anastasia;Frostegard, Johan

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目的:为确定抗磷酸胆碱(PC)和氧化低密度脂蛋白(OxLDL)抗体在动脉粥样硬化(Atherosclerosis,AS)发生中的重要性,方法和结果:226例确诊为高血压(舒张压> 95 mmHg)的患者来自欧洲拉西地平动脉粥样硬化研究。用ELISA法检测抗PC(aPC)、铜氧化(ox)或丙二醛(MDA)修饰的LDL的IgG和IgM亚类抗体。超敏C-反应蛋白通过散射比浊法测定,作为动脉粥样硬化的替代指标,我们使用了在入选时和入选后4年通过超声检查确定的颈总动脉和分叉远端壁的最大内膜中层厚度(IMT)的平均值。aPC可被PC和OxLDL竞争,而心磷脂(CL)和β 2-糖蛋白I(β 2GPI)的作用较小,而磷脂酰丝氨酸(PS)则完全不起作用。随访时IMT增加在入组时具有高IgM aPC的受试者中不太常见。(第75位和第90位;比值比:0.46; Cl:0.25-0.85; 0.36; Cl:0.15-0.87)和高IgM aOxLDL和aMDA-LDL(第90位;比值比0.27; p = 0.01; CI:0.11-0.69和0.27; p = 0.01; CI:0.11-0.69)。CRP与IMT变化无关。IgM aPC、aOxLDL和aMDA-LDL与IMT变化之间的关系与年龄、阿替洛尔或拉西地平治疗、吸烟和血脂无关。女性的IgM抗体水平较高(p < 0.05)。结论:高水平的抗PC和OxLDL IgM抗体预示着高血压患者颈动脉粥样硬化的发生。这些抗体是否可以用于治疗值得进一步研究。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Objective: To determine the importance of antibodies against phosphorylcholine (PC) and oxidized low density lipoprotein (OxLDL) for development of atherosclerosis.Methods and results: Two hundred and twenty six individuals with established hypertension (diastolic pressure > 95 mmHg) were from European Lacidipine Study on Atherosclerosis. Antibodies of IgG and IgM subclass were tested by ELISA against PC (aPC), cupper-oxidized (ox)- or malondialdehyde (MDA)-modified LDL. High-sensitivity C-reactive protein was measured by nephelometry.As a surrogate measure of atherosclerosis, we used the mean of the maximum intima-media thicknesses (IMT) in the far walls of common carotids and bifurcations was determined by ultrasonography at the time of enrolment, and 4 years following enrolment. aPC could be competed out by PC and OxLDL, while cardiolipin (CL) and beta 2-glycoprotein I (beta 2GPI) were less effective and phosphatidylserine (PS) not at all. Increases in IMT at follow-up were less common in subjects which at the time of enrolment had high IgM aPC (both 75th and 90th; odds ratios: 0.46; Cl: 0.25-0.85; 0.36; Cl: 0.15-0.87) and high IgM aOxLDL and aMDA-LDL (90th; odds ratios 0.27; p = 0.01; Cl: 0.11-0.69 and 0.27; p = 0.01; Cl: 0.11-0.69). CRP was unrelated to IMT-changes. The relationship between IgM aPC, aOxLDL and aMDA-LDL and changes in IMT was independent of age, treatment with atenolol or lacidipine, smoking and lipids. Women had higher levels of IgM antibodies tested (p < 0.05).Conclusions: High levels of IgM-antibodies against PC and OxLDL predict a favourable outcome in the development of carotid atherosclerosis in hypertensive subjects. Whether these antibodies could be used therapeutically deserves further study. (c) 2005 Elsevier Ireland Ltd. All rights reserved.