Division of Biological Chemistry, Department of Pharmaceutical Sciences Showa University School of Pharmacy, Shinagawa-ku, Tokyo 142-8555, Japan.
Division of Cardiology, Department of Medicine Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8555, Japan.
J Lipid Res. 2020 Jun;61(6):816-829. doi: 10.1194/jlr.RA119000312. Epub 2020 Apr 14.
Oxidized LDL (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized PC (oxPC) mAb, was recovered in flow-through and electronegative LDL [LDL(-)] fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in the LDL(-) fraction, present in patients with acute MI was 3-fold higher than that observed in healthy subjects. Surprisingly, the LDL(-) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(-) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues identified in apoB. The amount of oxPC adducts of apoB was higher in the LDL(-) than in the L1 fraction, as determined using Western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(-) fraction with an anti-oxPC mAb. The majority of PC species were not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.
氧化型低密度脂蛋白(oxLDL)是动脉粥样硬化形成的已知危险因素。本研究旨在揭示与人动脉粥样硬化形成相关的存在于人体循环中的 oxLDL 的结构特征。当 LDL 在阴离子交换柱上进行分级时,通过抗氧化型 PC(oxPC)mAb 检测到的体内氧化型 LDL(in vivo-oxLDL)存在于流通过程和电负性 LDL [LDL(-)] 级分中。急性心肌梗死患者体内电负性 in vivo-oxLDL(即 LDL(-) 级分中的 oxLDL)的数量比健康受试者高 3 倍。令人惊讶的是,LDL(-) 级分除了载脂蛋白 B(apoB)外还含有载脂蛋白 A1(apoA1),并且用透射电子显微镜观察到 HDL 大小的颗粒。在 LDL(-) 级分中,鉴定到在 apoA1 的所有赖氨酸残基上均存在丙烯醛加合物,而在 apoB 上仅鉴定到少量的丙烯醛修饰残基。用 Western blot 法测定,apoB 的 oxPC 加合物在 LDL(-) 级分中的含量高于 L1 级分。电负性体内氧化型 LDL 是用抗 oxPC mAb 从 LDL(-) 级分中免疫纯化的。大多数 PC 种类没有被氧化,而 oxPC 和溶血 PC 没有积累。在这里,我们提出在人体循环血浆中有两种类型的体内氧化型 LDL,并且电负性体内氧化型 LDL 伴随着氧化型 HDL。