Steinerová A, Racek J, Stozický F, Zima T, Fialová L, Lapin A
Medika Centrum, Charles University Hospital, Pilsen, Czech Republic.
Physiol Res. 2001;50(2):131-41.
Modification of low density lipoprotein (LDL) particles due to oxidation, glycation and binding of advanced glycation end-products (AGEs) or malondialdehyde (MDA, a final product of lipid peroxidation) is considered most important in the process of atherogenesis. Oxidatively modified LDL are distinguished by another receptor type, which was discovered on the surface of macrophages and was called the scavenger receptor. Uncontrolled intake of LDL converts macrophages to foam cells; their accumulation under the vascular endothelium is considered as the first stage of atherosclerosis. Oxidation of LDL is a complex process taking place in both the extra- and intracellular space. At the end of this oxidative process, modified LDL particles show chemotactic, cytotoxic and immunogenic properties. Oxidized LDL express a large number of epitopes and cause production of polyclonal autoantibodies against these products, especially against apoB100 modified by MDA and 4-hydroxynonenal. IgoxLDL (antibodies against oxidized LDL) can be demonstrated either directly in intimal lesions or as a component of circulating immune complexes. IgoxLDL do not form a homogeneous group but a varied mixture of antibodies-isoantibodies caused by HDL and LDL polymorphism, antibodies against the lipid phase of LDL and antibodies against modified apoB100 of the immunoglobulin class IgA or IgG. Antibodies against oxLDL were found in many diseases other than atherosclerosis such as diabetes mellitus, renovascular syndrome, uremia, rheumatic fever, morbus Bechtjerev or lupus erythematodes. Newborns have practically the same levels of IgoxLDL as their mothers; however, these values did not differ from those in the healthy population of non-pregnant women of the same age. The decrease in IgoxLDL titer was very slow and lasted many months; that is why this parameter cannot be considered suitable for describing the rapid changes during oxidative stress of the organism. Positive correlation of IgoxLDL with antiphospholipids and other antibodies was repeatedly demonstrated; their determination can thus be used as a marker for the description of total production of autoantibodies in various diseases. The changes and correlations of IgoxLDL, anti-beta-2-glycoprotein I IgG and antiphospholipid antibodies support the immunological link between thrombotic and atherosclerotic processes in the human body.
低密度脂蛋白（LDL）颗粒因氧化、糖基化以及与晚期糖基化终产物（AGEs）或丙二醛（MDA，脂质过氧化的终产物）结合而发生的修饰，在动脉粥样硬化形成过程中被认为是最为重要的。氧化修饰的LDL可通过另一种受体类型加以区分，该受体是在巨噬细胞表面发现的，被称为清道夫受体。LDL的无节制摄取会使巨噬细胞转变为泡沫细胞；它们在血管内皮细胞下的积聚被视为动脉粥样硬化的第一阶段。LDL的氧化是一个在细胞外和细胞内空间均会发生的复杂过程。在这个氧化过程结束时，修饰的LDL颗粒表现出趋化性、细胞毒性和免疫原性。氧化型LDL表达大量表位，并引发针对这些产物的多克隆自身抗体的产生，尤其是针对被MDA和4-羟基壬烯醛修饰的载脂蛋白B100。抗氧化型LDL抗体（IgoxLDL）既可以直接在内膜病变中检测到，也可以作为循环免疫复合物的一个组成部分被检测到。IgoxLDL并非形成一个同质群体，而是由HDL和LDL多态性引起的抗体-同种抗体、针对LDL脂质相的抗体以及针对免疫球蛋白IgA或IgG类修饰的载脂蛋白B100的抗体的多样混合物。除动脉粥样硬化外，在许多其他疾病中也发现了抗氧化型LDL抗体，如糖尿病、肾血管综合征、尿毒症、风湿热、贝赫切特病或红斑狼疮。新生儿的抗氧化型LDL抗体水平与他们的母亲几乎相同；然而，这些数值与同龄未怀孕健康女性群体的数值并无差异。抗氧化型LDL抗体滴度的下降非常缓慢，且持续数月之久；因此，这个参数并不适合用于描述机体氧化应激期间的快速变化。抗氧化型LDL抗体与抗磷脂抗体及其他抗体之间的正相关性已被反复证实；因此，它们的检测可作为描述各种疾病中自身抗体总产生情况的一个标志物。抗氧化型LDL抗体、抗β2糖蛋白I IgG和抗磷脂抗体的变化及相关性支持了人体血栓形成过程与动脉粥样硬化过程之间的免疫学联系。
