Itabe Hiroyuki, Sawada Naoko, Makiyama Tomohiko, Obama Takashi
Division of Biological Chemistry, Department of Pharmaceutical Sciences, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Tokyo 142-8555, Japan.
Biomedicines. 2021 Jun 8;9(6):655. doi: 10.3390/biomedicines9060655.
Oxidative modification of lipoproteins is implicated in the occurrence and development of atherosclerotic lesions. Earlier studies have elucidated on the mechanisms of foam cell formation and lipid accumulation in these lesions, which is mediated by scavenger receptor-mediated endocytosis of oxidized low-density lipoprotein (oxLDL). Mounting clinical evidence has supported the involvement of oxLDL in cardiovascular diseases. High-density lipoprotein (HDL) is known as anti-atherogenic; however, recent studies have shown circulating oxidized HDL (oxHDL) is related to cardiovascular diseases. A modified structure of oxLDL, which was increased in the plasma of patients with acute myocardial infarction, was characterized. It had two unique features: (1) a fraction of oxLDL accompanied oxHDL, and (2) apoA1 was heavily modified, while modification of apoB, and the accumulation of oxidized phosphatidylcholine (oxPC) and lysophosphatidylcholine (lysoPC) was less pronounced. When LDL and HDL were present at the same time, oxidized lipoproteins actively interacted with each other, and oxPC and lysoPC were transferred to another lipoprotein particle and enzymatically metabolized rapidly. This brief review provides a novel view on the dynamics of oxLDL and oxHDL in circulation.
脂蛋白的氧化修饰与动脉粥样硬化病变的发生和发展有关。早期研究阐明了这些病变中泡沫细胞形成和脂质积累的机制,这是由清道夫受体介导的氧化低密度脂蛋白(oxLDL)的内吞作用介导的。越来越多的临床证据支持oxLDL参与心血管疾病。高密度脂蛋白(HDL)被认为具有抗动脉粥样硬化作用;然而,最近的研究表明循环氧化HDL(oxHDL)与心血管疾病有关。对急性心肌梗死患者血浆中增加的oxLDL的修饰结构进行了表征。它有两个独特的特征:(1)一部分oxLDL与oxHDL相伴,(2)载脂蛋白A1被大量修饰,而载脂蛋白B的修饰以及氧化磷脂酰胆碱(oxPC)和溶血磷脂酰胆碱(lysoPC)的积累则不太明显。当LDL和HDL同时存在时,氧化脂蛋白会积极地相互作用,oxPC和lysoPC会转移到另一个脂蛋白颗粒上并迅速进行酶促代谢。这篇简短的综述提供了关于循环中oxLDL和oxHDL动态变化的新观点。