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在急性心肌梗死患者中增加的循环氧化 LDL 伴随着大量修饰的 HDL。

Circulating oxidized LDL, increased in patients with acute myocardial infarction, is accompanied by heavily modified HDL.

机构信息

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.

出版信息

J Lipid Res. 2020 Jun;61(6):816-829. doi: 10.1194/jlr.RA119000312. Epub 2020 Apr 14.

Abstract

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.

摘要

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。

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