Oxidized lipoproteins released from atherosclerotic lesions

我们用一种新型的抗OXLDL的单抗(FOHLA/DLH3)和一种抗载脂蛋白B的多克隆抗体建立了一种检测OXLDL水平的夹心ELISA法。FOLA/DLH3是氧化低密度脂蛋白的特异性抗原，不与天然的、乙酰化的、丙二醛处理的或糖化的低密度脂蛋白结合。用这种高灵敏度的新方法，我们检测了急性心肌梗死(AMI)、不稳定型心绞痛(UAP)和稳定性心绞痛(SAP)患者的OXLDL水平。此外，我们用免疫组织化学方法研究了冠状动脉粥样硬化切除标本中oxLDL的存在，这些标本取自导致SAP和UAP的罪魁祸首病变，尽管这些患者的oxLDL水平尚不清楚。因此，这项研究是基于一组临床特征相似但应用了不同方法的患者。第一组包括有不同程度冠脉综合征体征和症状的患者，测定了oxLDL水平，并与该综合征的严重程度相关。第二组患者也表现为心绞痛，但在这些患者中，只有从罪犯病变中获得的动脉粥样硬化标本可用，并对OXLDL的存在进行了免疫组织化学研究。结论：本研究表明，OXLDL水平与急性冠脉综合征的严重程度呈显著正相关，且病变越严重，OXLDL阳性巨噬细胞的比例也显著增加。这些观察结果表明，OXLDL水平的升高与人类冠状动脉粥样硬化病变的斑块不稳定性有关。

We developed a sandwich ELISA method to measure OXLDL levels using a novel anti-OXLDL monoclonal antibody (FOHla/DLH3) and an anti-apolipoprotein B polyclonal antibody. FOHla/DLH3 is specific for ox-LDL and does not bind to native, acetylated, MDA-treated, or glycated LDL.With the use of this new and highly sensitive method, we measured the levels of OXLDL in patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP), and stable angina pectoris (SAP). In addition, we immuno-histochemically studied the presence of oxLDL in coronary atherectomy specimens taken from the culprit lesions responsible for SAP and UAP, although oxLDL levels in these patients were not available. Hence, the study is based on a cohort of patients with similar clinical characteristics but in whom different methodologies were applied. The first group contains patients presenting with various degrees of signs and symptoms of a coronary syndrome in whom oxLDL levels were determined and correlated with the severity of the syndrome. The second group of patients also presented with angina pectoris, but in those patients, only atherectomy specimens obtained from culprit lesions were available and studied immuno-histochemically for the presence of oxLDL.In conclusions, this study demonstrates that OXLDL levels show a significant positive correlation with the severity of acute coronary syndromes and that the more severe lesions also contain a significantly higher percentage of OXLDL positive macrophages. These observations suggest that increased levels of OXLDL relate to plaque instability in human coronary atherosclerotic lesions.