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针对磷酸胆碱和氧化低密度脂蛋白的IgM亚类抗体是高血压患者动脉粥样硬化的保护因素。

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

作者信息

Su Jun, Georgiades Anastasia, Wu Ruihua, Thulin Thomas, de Faire Ulf, Frostegård Johan

机构信息

Center of Infectious Medicine and Unit of Rheumatology, F 59 Department of Medicine, Karolinska University Hospital, Huddinge, Stockholm 141 86, Sweden.

出版信息

Atherosclerosis. 2006 Sep;188(1):160-6. doi: 10.1016/j.atherosclerosis.2005.10.017. Epub 2005 Nov 22.

Abstract

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 > 95mmHg) 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 beta2-glycoprotein I (beta2GPI) 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; CI: 0.25-0.85; 0.36; CI: 0.15-0.87) and high IgM aOxLDL and aMDA-LDL (90th; odds ratios 0.27; p = 0.01; CI: 0.11-0.69 and 0.27; p = 0.01; CI: 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.

摘要

目的

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发展中的重要性。

方法与结果

226例确诊高血压(舒张压>95mmHg)患者来自欧洲拉西地平动脉粥样硬化研究。采用酶联免疫吸附测定法(ELISA)检测IgG和IgM亚类抗体针对PC(aPC)、铜氧化(ox)或丙二醛(MDA)修饰的低密度脂蛋白。采用散射比浊法测定高敏C反应蛋白。作为动脉粥样硬化的替代指标,我们使用颈总动脉远壁和分叉处最大内膜中层厚度(IMT)的平均值,在入组时和入组后4年通过超声检查确定。aPC可被PC和OxLDL竞争抑制,而心磷脂(CL)和β2-糖蛋白I(β2GPI)的作用较弱,磷脂酰丝氨酸(PS)则完全无效。在入组时具有高IgM aPC(第75和90百分位数;优势比:0.46;可信区间:0.25 - 0.85;0.36;可信区间:0.15 - 0.87)以及高IgM aOxLDL和aMDA - LDL(第90百分位数;优势比0.27;p = 0.01;可信区间:0.11 - 0.69和0.27;p = 0.01;可信区间:0.11 - 0.69)的受试者,随访时IMT增加的情况较少见。CRP与IMT变化无关。IgM aPC、aOxLDL和aMDA - LDL与IMT变化之间的关系独立于年龄、阿替洛尔或拉西地平治疗、吸烟和血脂水平。女性检测到的IgM抗体水平较高(p < 0.05)。

结论

高血压患者中,高水平的抗PC和OxLDL IgM抗体预示着颈动脉粥样硬化发展的良好结局。这些抗体是否可用于治疗值得进一步研究。

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