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Oxidized lipoproteins released from atherosclerotic lesions

动脉粥样硬化病变释放的氧化脂蛋白

基本信息

批准号：
12672121
负责人：
TAKANO Tatsuya
金额：
$ 2.43万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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.

我们开发了一种夹心ELISA方法，使用新的抗OXLDL单克隆抗体（FOHla/DLH 3）和抗载脂蛋白B多克隆抗体来测量OXLDL水平。FOH 1a/DLH 3对ox-LDL具有特异性，不与天然的、乙酰化的、MDA处理的或糖化的LDL结合，利用这种新的和高度敏感的方法，我们测定了急性心肌梗死（AMI）、不稳定型心绞痛（UAP）和稳定型心绞痛（SAP）患者的OXLDL水平。此外，我们免疫组化研究了从SAP和UAP的罪犯病变中提取的冠状动脉粥样硬化斑块切除术标本中oxLDL的存在，尽管这些患者的oxLDL水平不可用。因此，该研究基于具有相似临床特征但应用不同方法的患者队列。第一组包含表现出不同程度的冠状动脉综合征体征和症状的患者，其中oxLDL水平被确定并与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，只有从罪犯病变获得的斑块切除术标本可用，并对oxLDL的存在进行免疫组织化学研究。这项研究表明，OXLDL水平与急性冠状动脉综合征的严重程度呈显著正相关，病变越严重，OXLDL阳性的百分比也越高巨噬细胞这些观察结果表明，增加的OXLDL水平与人冠状动脉粥样硬化病变斑块的不稳定性。