Fredrikson Gunilla Nordin, Söderberg Ingrid, Lindholm Marie, Dimayuga Paul, Chyu Kuang-Yuh, Shah Prediman K, Nilsson Jan
Department of Medicine, Malmö University Hospital, Lund University, Malmö, Sweden.
Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):879-84. doi: 10.1161/01.ATV.0000067937.93716.DB. Epub 2003 Mar 20.
LDL oxidation is believed to play an important role in the development of atherosclerosis, and oxidized LDL particles have been shown to become targets for the immune system. Immunization of animals with oxidized LDL results in reduction of atherosclerosis, suggesting an atheroprotective effect of this immune response.
Using a polypeptide library covering the complete sequence of apoB-100, a large number of native and malondialdehyde-modified peptide sequences in apoB-100 that are recognized by antibodies in human plasma were identified. We report here that immunization with apoB-100 peptide sequences, against which high levels of IgG and IgM antibodies are present in healthy human controls, reduce atherosclerosis in apoE-null mice by about 60%. Immunizations with these peptides were also found to increase the collagen content of subvalvular lesions.
These studies have identified peptide sequences in apoB-100 that induce immune responses, which inhibits atherosclerosis. This suggests a way of developing an immunization therapy for coronary heart disease.
低密度脂蛋白（LDL）氧化被认为在动脉粥样硬化的发展中起重要作用，并且氧化的LDL颗粒已被证明成为免疫系统的靶标。用氧化LDL对动物进行免疫可导致动脉粥样硬化减轻，提示这种免疫反应具有抗动脉粥样硬化作用。
利用覆盖载脂蛋白B-100完整序列的多肽文库，鉴定出大量载脂蛋白B-100中被人血浆抗体识别的天然和丙二醛修饰的肽序列。我们在此报告，用健康人对照中存在高水平IgG和IgM抗体的载脂蛋白B-100肽序列进行免疫，可使载脂蛋白E基因敲除小鼠的动脉粥样硬化减轻约60%。还发现用这些肽进行免疫可增加瓣膜下病变的胶原含量。
这些研究已鉴定出载脂蛋白B-100中可诱导免疫反应的肽序列，该免疫反应可抑制动脉粥样硬化。这提示了一种开发冠心病免疫治疗方法的途径。
