Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes
Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes
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DOI：
10.1016/s0735-1097(02)02769-9
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发表时间：
2003-02-05
影响因子：
24
通讯作者：
Witztum, JL
中科院分区：
文献类型：
--
作者：
Tsimikas, S;Bergmark, C;Witztum, JL
目的探讨氧化低密度脂蛋白(OxLDL)血浆标志物反映急性冠脉综合征(ACS)的假设。背景氧化型低密度脂蛋白参与动脉粥样硬化的发病机制，但其在ACS中的作用尚未确定。方法前瞻性采集急性心肌梗死(MI)(n=8)、不稳定型心绞痛(UA)(n=15)、稳定型冠状动脉疾病(CAD)(n=17)、冠状动脉造影正常(n=8)和健康人(n=18)的血浆样本。30天、120天和210天。采用化学发光酶联免疫吸附分析法检测血浆中NO的含量。1)免疫球蛋白(Ig)M和Ig G氧化低密度脂蛋白自身抗体滴度(以4个不同表位的平均值表示)；2)低密度脂蛋白自身抗体免疫复合物(L DL-IC)；3)抗体E06测定的最低氧化低密度脂蛋白(Ox L DL-E06)，由载脂蛋白B-0.0001的氧化磷脂(OxPL)含量确定。在30天的随访中，MI组和UA组的平均IgM OxLDL滴度分别增加了48%(p<；0.001)和20%(p<；0.001)，IgM低密度脂蛋白-IC分别增加了60%(p<；0.01)和26%(p<；0.01)。MI组出院时OxLDL-E06水平升高54%(p<；0.01)，30天时升高36%。在其他组中，没有注意到任何OxLDL标志物的显著变化。在MI组，OxLDL-E06水平与脂蛋白(A)或Lp(A)的急剧上升强烈平行，这表明有毒的OxPL优先与Lp(A)结合。在整个队列患者中，氧化型低密度脂蛋白-E06与Lp(A)的相关性也非常好(r=0.91p<；0.0001)。结论循环中的氧化低密度脂蛋白特异性标志物强烈反映了急性冠脉综合征的存在，意味着对新暴露的氧化特异性表位的免疫意识以及循环中可能释放的氧化低密度脂蛋白。OxLDL-E06测量为斑块破裂和Lp(A)的潜在致动脉粥样硬化提供了新的见解。
OBJECTIVES This study was conducted to test the hypothesis that plasma markers of oxidized low-density lipoprotein (OxLDL) reflect acute coronary syndromes (ACS).BACKGROUND Oxidized LDL contributes to the pathogenesis of atherosclerosis, but its role in ACS is not established.METHODS Serial plasma samples were prospectively obtained from patients with an acute myocardial infarction (MI) (n = 8), unstable angina (UA) (n 15), stable coronary artery disease (CAD) (n = 17), angiographically normal coronary arteries (n = 8), and from healthy subjects (n 18), at entry into the study, hospital discharge (MI group only), and at 30, 120, and 210 days. Chemiluminescent enzyme-linked immunosorbent assay was used to quantitate plasma levels of. 1) immunoglobulin (Ig)M and IgG OxLDL autoantibody titers (presented as a mean OxLDL autoantibody titer by averaging the results of four distinct epitopes); 2) LDL-autoantibody immune complexes (LDL-IC); and 3) minimally OxLDL measured by antibody E06 (OxLDL-E06), as determined by the content of oxidized phospholipids (OxPL) per apolipoprotein B-100.RESULTS Baseline OxLDL, IgG autoantibody levels were higher in the MI group (p < 0.0001). At 30-day follow-up, the mean IgM OxLDL titers increased by 48% (p < 0.001) and 20% (p < 0.001), and IgM LDL-IC increased by 60% (p < 0.01) and 26% (p < 0.01) in the MI and UA groups, respectively. The OxLDL-E06 levels increased by 54% (p < 0.01) in the MI group at hospital discharge and by 36% at 30 days. No significant changes in any OxLDL markers were noted in the other groups. The OxLDL-E06 levels strongly paralleled the acute rise in lipoprotein(a), or Lp(a), in the MI group, suggesting that toxic OxPL are preferentially bound to Lp(a). Oxidized LDL-E06 also correlated extremely well with Lp(a) in the entire cohort of patients (r = 0.91, p < 0.0001).CONCLUSIONS Circulating OxLDL-specific markers strongly reflect the presence of ACS, implying immune awareness to newly exposed oxidation-specific epitopes and possible release of OxLDL in the circulation. The OxLDL-E06 measurements provide novel insights into plaque rupture and the potential atherogenicity of Lp(a).