Salonen J T, Ylä-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R, Nyyssönen K, Palinski W, Witztum J L
Research Institute of Public Health, University of Kuopio, Finland.
Lancet. 1992 Apr 11;339(8798):883-7. doi: 10.1016/0140-6736(92)90926-t.
Oxidative modification of LDL renders it immunogenic and autoantibodies to epitopes of oxidised LDL, such as malondialdehyde (MDA)-lysine, are found in serum and recognise material in atheromatous tissue. However, there has been no prospective study to assess the importance of oxidised LDL among patients with vascular disease. We compared the titre of autoantibodies to MDA-modified LDL and native LDL in baseline serum samples of 30 eastern Finnish men with accelerated two-year progression of carotid atherosclerosis and 30 age-matched controls without progression. Neither group had specific antibody binding to native LDL. A titre was defined as a ratio of antibody binding to MDA-LDL/binding to native LDL. Cases had a significantly higher titre to MDA-LDL (2.67 vs 2.06, p = 0.003). Cases also had a greater proportion of smokers (37% vs 3%), higher LDL cholesterol (4.2 mmol/l vs 3.6 mmol/l), and higher serum copper concentration (1.14 mg/l vs 1.04 mg/l). Even after adjusting for these variables and the severity of baseline atherosclerosis, the difference in antibody titre remained significant in a multifactorial logistic model (p = 0.031). Thus, the titre of autoantibodies to MDA-LDL was an independent predictor of the progression of carotid atherosclerosis in these Finnish men. Our data provide further support for a role of oxidatively modified LDL in atherogenesis.
低密度脂蛋白（LDL）的氧化修饰使其具有免疫原性，血清中可发现针对氧化型LDL表位的自身抗体，如丙二醛（MDA）-赖氨酸抗体，且这些抗体可识别动脉粥样硬化组织中的物质。然而，尚无前瞻性研究评估氧化型LDL在血管疾病患者中的重要性。我们比较了30名芬兰东部男性颈动脉粥样硬化加速进展患者与30名年龄匹配的无进展对照者的基线血清样本中，针对MDA修饰的LDL和天然LDL的自身抗体滴度。两组均无针对天然LDL的特异性抗体结合。滴度定义为抗体与MDA-LDL结合/与天然LDL结合的比值。病例组针对MDA-LDL的滴度显著更高（2.67对2.06，p = 0.003）。病例组吸烟者比例也更高（37%对3%），低密度脂蛋白胆固醇水平更高（4.2 mmol/l对3.6 mmol/l），血清铜浓度更高（1.14 mg/l对1.04 mg/l）。即使在对这些变量以及基线动脉粥样硬化的严重程度进行校正后，在多因素逻辑模型中抗体滴度的差异仍具有显著性（p = 0.031）。因此，针对MDA-LDL的自身抗体滴度是这些芬兰男性颈动脉粥样硬化进展的独立预测因子。我们的数据进一步支持了氧化修饰的LDL在动脉粥样硬化发生中的作用。
