Maggi E, Marchesi E, Ravetta V, Martignoni A, Finardi G, Bellomo G
Department of Internal Medicine and Medical Therapeutics, IRCCS Policlinico San Matteo, University of Pavia, Italy.
J Hypertens. 1995 Jan;13(1):129-38.
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.
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.
An enzyme-linked immunosorbent assay method was employed, using native LDL, Cu(2+)-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 absolute values.
The patients with essential hypertension had an antibody ratio significantly higher than control subjects with respect to anti-Cu(2+)-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-Cu(2+)-oxidized LDL antibody titres. The anti-MDA human serum albumin antibody titre was not different in the two groups of patients. An inverse correlation was detected between the anti-MDA-LDL immunoglobulin M titre and the age of the patients.
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.
我们之前曾报道，从原发性高血压患者中分离出的低密度脂蛋白（LDL）比从血压正常的对照受试者中分离出的脂蛋白在体外更易被氧化。在本研究中，我们调查了高血压患者体内LDL氧化的情况。
抗氧化修饰的LDL自身抗体的存在被视为体内LDL氧化的合适指标，因为氧化修饰后，LDL会表达引发免疫反应的抗原表位。在新诊断的原发性高血压未治疗患者的血浆中测量抗体滴度。
采用酶联免疫吸附测定法，使用天然LDL、铜（2+）氧化的LDL和丙二醛衍生的LDL（MDA-LDL）作为抗原。还使用人血清白蛋白和MDA人血清白蛋白来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抗原与抗天然抗原绝对值之比。
原发性高血压患者针对抗铜（2+）氧化LDL免疫球蛋白G和M以及抗MDA-LDL免疫球蛋白G和M的抗体比值显著高于对照受试者。抗MDA-LDL和抗铜（2+）氧化LDL抗体滴度之间存在显著正相关。两组患者的抗MDA人血清白蛋白抗体滴度无差异。检测到抗MDA-LDL免疫球蛋白M滴度与患者年龄呈负相关。
所得结果与以下观点一致，即在高血压发展的早期阶段，LDL会发生体内氧化，这通过针对氧化LDL表位的自身抗体的产生得以体现。氧化过程似乎对LDL具有特异性，可能与高血压的进展以及常使高血压本身复杂化的动脉粥样硬化的发展都有关。
