Experimental Immunology Laboratory, Section of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Free Radic Biol Med. 2010 Nov 30;49(10):1480-6. doi: 10.1016/j.freeradbiomed.2010.08.001. Epub 2010 Aug 6.
Antibodies to malondialdehyde (MDA)-modified macromolecules (adducts) have been detected in the serum of patients with atherosclerosis and correlate with the progression of this disease. However, the epitope and its formation have not been characterized. Studies have shown that excess MDA can be degraded to acetaldehyde, which combines with proteins to from a stable dihydropyridine adduct. To investigate, mice were immunized with MDA adducts in the absence of adjuvant and showed an increase in antibodies to MDA adducts and the carrier protein as the concentration of MDA was increased. In fact, a number of the commercially available antibodies to MDA-modified proteins were able to be inhibited by a chemical analogue, hexyl-MAA. Also, MDA-MAA adducts were detected in the serum and aortic tissue of JCR diabetic/atherosclerotic rats. These studies determined that commercially available antibodies to MDA predominantly react with the MAA adduct and are present in the JCR model of atherosclerosis in both the serum and the aortic tissue. Therefore, the immune response to MDA-modified proteins is most probably to the dihydropyridine structure (predominant epitope in MAA), which suggests that MAA adducts may play a role in the development and/or progression of atherosclerosis.
抗丙二醛（MDA）修饰大分子（加合物）的抗体已在动脉粥样硬化患者的血清中被检测到，并且与该疾病的进展相关。然而，其抗原表位及其形成尚未被阐明。研究表明，过量的 MDA 可以被降解为乙醛，乙醛与蛋白质结合形成稳定的二氢吡啶加合物。为了进行研究，用 MDA 加合物对没有佐剂的小鼠进行免疫，结果显示随着 MDA 浓度的增加，抗体对 MDA 加合物和载体蛋白的增加。事实上，许多市售的 MDA 修饰蛋白抗体可以被化学类似物己基-MAA 抑制。此外，在 JCR 糖尿病/动脉粥样硬化大鼠的血清和主动脉组织中也检测到 MDA-MAA 加合物。这些研究表明，市售的 MDA 抗体主要与 MAA 加合物反应，并且在 JCR 动脉粥样硬化模型中存在于血清和主动脉组织中。因此，对 MDA 修饰蛋白的免疫反应很可能是针对二氢吡啶结构（MAA 中的主要抗原表位），这表明 MAA 加合物可能在动脉粥样硬化的发生和/或进展中起作用。
