Presence of autoantibodies against oxidatively modified low‐density lipoprotein in essential hypertension: a biochemical signature of an enhanced in vivo low‐density lipoprotein oxidation
Presence of autoantibodies against oxidatively modified low‐density lipoprotein in essential hypertension: a biochemical signature of an enhanced in vivo low‐density lipoprotein oxidation
复制标题
原发性高血压中存在针对氧化修饰低密度脂蛋白的自身抗体：体内低密度脂蛋白氧化增强的生化特征
作者：
E. Maggi;E. Marchesi;V. Ravetta;A. Martignoni;G. Finardi;G. Bellomo
目的研究原发性高血压患者的低密度脂蛋白（LDL）在体外氧化反应中的敏感性。在本研究中，我们调查了高血压患者体内LDL氧化的发生。抗氧化修饰的LDL自身抗体的存在被认为是体内LDL氧化的合适指标，因为在氧化修饰后，LDL表达引发免疫应答的抗原表位。抗体滴度测定血浆未经治疗的新诊断原发性高血压患者。方法采用酶联免疫吸附法，分别以天然LDL、Cu 2+氧化LDL和丙二醛衍生LDL（MDA-LDL）为抗原。人血清白蛋白和MDA人血清白蛋白也用于监测与其他氧化分子的交叉反应性。抗体滴度表示为抗修饰和抗天然抗原绝对值之间的比率。结果原发性高血压患者血清中抗Cu 2+氧化LDL免疫球蛋白G、M和抗MDA-LDL免疫球蛋白G、M的抗体比率均显著高于对照组。抗MDA-LDL抗体滴度与抗Cu ~（2+）氧化LDL抗体滴度呈显著正相关。抗MDA人血清白蛋白抗体滴度两组间无差异。抗MDA-LDL免疫球蛋白M滴度与患者年龄呈负相关。结论所获得的结果是一致的，在高血压发展的早期阶段，LDL进行体内氧化，这是反映了对氧化LDL的表位的自身抗体的产生。氧化过程似乎是LDL特有的，可能与高血压的进展和动脉粥样硬化的发展有关，动脉粥样硬化往往使高血压本身复杂化。
Objective We have previously reported that low-density lipoproteins (LDL) isolated from patients with essential hypertension are more susceptible to in vitro oxidation than lipoproteins isolated from normotensive control subjects. In the present study we investigated the occurrence of in vivo LDL oxidation in hypertensive patients. Design The presence of antioxidatively modified LDL autoantibodies was taken as a suitable index of in vivo LDL oxidation because, after oxidative modifications, LDL express antigenic epitopes that elicit an immune response. The antibody titres were measured in plasma from untreated patients with newly diagnosed essential hypertension. Methods An enzyme-linked immunosorbent assay method was employed, using native LDL, Cu2+-oxidized LDL and malondialdehyde-derivatized LDL (MDA-LDL) as antigens. Human serum albumin and MDA human serum albumin were also used to monitor cross-reactivity with other oxidized molecules. The antibody titre was expressed as the ratio between anti-modified and anti-native antigen absolule values. Results The patients with essential hypertension had an antibody ratio significantly higher than control subjects with respect to anti-Cu2+-oxidized LDL immunoglobulins G and M, and with respect to anti-MDA-LDL immunoglobulins G and M. A significant positive correlation was found between anti-MDA-LDL and anti-Cu2+-oxidized LDL antibody titres. The anti-MDA human serum albumin antibody titre was not different in the two groups of palients. An inverse correlation was detected between the anti-MDA-LDL immunoglobulin M titre and the age of the patients. Conclusions The results obtained are consistent with the view that, during the early phases of hypertension development, LDL undergo in vivo oxidation that is mirrored by the generation of autoantibodies against epitopes of oxidized LDL. The oxidation process appears specific for LDL and might be relevant both for the progression of hypertension and for the development of the atherosclerosis that often complicates hypertension itself.