Faviou Elsa, Vourli Georgia, Nounopoulos Charalampos, Zachari Ariadni, Dionyssiou-Asteriou Amalia
Department of Clinical Biochemistry, Medical School, University Hospital Attikon, 1 Rimini Street, 12462 Chaidari, Athens, Greece.
Free Radic Res. 2005 Apr;39(4):419-29. doi: 10.1080/10715760500072156.
The oxidative hypothesis of atherosclerosis proposes that oxidative modification of low density lipoprotein (LDL) plays a critical role in atherogenesis. The evaluation of LDL oxidation in vivo is therefore very important. However, data concerning the evaluation of the above biochemical marker is very limited in clinical practice. This study was conducted to test the hypothesis that plasma levels of ox-LDL reflect atherosclerosis and determine the clinical significance in the measurement of circulating ox-LDL and autoantibodies against them as well as their correlation with homocysteine and lipid parameters in the diagnosis and severity of coronary heart disease. A total of 273 individuals were examined: 41 suffering from unstable angina pectoris (UAP), 62 from stable angina pectoris (SAP) and 170 healthy control subjects. We used a sensitive method for detecting ox-LDL that is based on a direct sandwich technique (ELISA) in which two monoclonal antibodies are directed against separate antigenic determinants on the oxidized apolipoprotein-B molecule along with another enzyme immunoassay designed to determine human antibodies to oxidized LDL (anti-oxLDL) directly in serum. Total homocysteine (HCY) was evaluated by means of a fully automated fluorescence polarization immunoassay. Patients with UAP exhibited marked elevations in oxLDL levels as compared to patients with SAP (161.2 +/- 28.4 vs. 119.2 +/- 26.6, p < 0.001) and the control subjects (67 +/- 18.8, p < 0.001). The difference in oxLDL levels between patients with SAP and the control group was also statistically significant. Similarly, patients with UAP showed marked elevations in anti-oxLDL antibodies compared to both patients with SAP (602.2 +/- 62.2 vs. 510.8 +/- 50.3,p < 0.001) and control subjects (368 +/- 79.6, p < 0.001). The difference in anti-oxLDL levels between patients with SAP and the controls was also statistically significant. OxLDL levels were not correlated with age in any of the groups studied. Triglycerides, LDL-cholesterol and total cholesterol were elevated in patients with UAP as opposed to patients with SAP and the control subjects, while HDL levels were elevated in the control subjects when compared to patients with SAP and UAP. Homocysteine levels were elevated in patients suffering from UAP and SAP when compared to healthy subjects. Patients with UAP or SAP did not differ on homocysteine levels. Our findings demonstrate the presence of oxLDL in vivo, its strong association with coronary artery disease as well as with the severity of the clinical presentation.
动脉粥样硬化的氧化假说提出，低密度脂蛋白（LDL）的氧化修饰在动脉粥样硬化形成中起关键作用。因此，体内LDL氧化的评估非常重要。然而，在临床实践中，关于上述生化标志物评估的数据非常有限。本研究旨在检验以下假说：血浆氧化型LDL（ox-LDL）水平反映动脉粥样硬化，并确定循环ox-LDL及其自身抗体测量的临床意义，以及它们与同型半胱氨酸和脂质参数在冠心病诊断和严重程度方面的相关性。共检查了273人：41例不稳定型心绞痛（UAP）患者、62例稳定型心绞痛（SAP）患者和170名健康对照者。我们使用一种基于直接夹心技术（ELISA）的灵敏方法检测ox-LDL，其中两种单克隆抗体针对氧化载脂蛋白B分子上不同的抗原决定簇，另一种酶免疫测定法用于直接测定血清中针对氧化LDL的人抗体（抗oxLDL）。总同型半胱氨酸（HCY）通过全自动荧光偏振免疫测定法进行评估。与SAP患者（161.2±28.4 vs. 119.2±26.6，p<0.001）和对照组（67±18.8，p<0.001）相比，UAP患者的oxLDL水平显著升高。SAP患者与对照组之间的oxLDL水平差异也具有统计学意义。同样，与SAP患者（602.2±62.2 vs. 510.8±50.3，p<0.001）和对照组（）相比，UAP患者的抗oxLDL抗体显著升高。。SAP患者与对照组之间的抗oxLDL水平差异也具有统计学意义。在任何研究组中，oxLDL水平均与年龄无关。与SAP患者和对照组相比UAP患者的甘油三酯、低密度脂蛋白胆固醇和总胆固醇升高，而与SAP患者和UAP患者相比，对照组的高密度脂蛋白水平升高。与健康受试者相比，UAP和SAP患者的同型半胱氨酸水平升高。UAP或SAP患者的同型半胱氨酸水平无差异。我们的研究结果表明体内存在oxLDL，它与冠状动脉疾病以及临床表现的严重程度密切相关。
