Heinecke J W
Division of Atherosclerosis, Nutrition and Lipid Research, St Louis, MO 63110, USA.
Curr Opin Lipidol. 1997 Oct;8(5):268-74. doi: 10.1097/00041433-199710000-00005.
Oxidatively damaged LDL may play a critical role in the pathogenesis of atherosclerotic vascular disease. Several pathways promote LDL oxidation in vitro but the physiologically relevant mechanisms have proven difficult to identify. Detection of stable compounds that result from specific reaction pathways has provided the first insights into the mechanism of oxidative damage in the human artery wall. Mass spectrometric analysis of protein oxidation products isolated from atherosclerotic tissue implicate tyrosyl radical, reactive nitrogen intermediates and hypochlorous acid in LDL oxidation and lesion formation in vivo. Hypochlorous acid is only generated by the phagocytic enzyme myeloperoxidase, which can also generate tyrosyl radical and reactive nitrogen intermediates. Chiral phase high-pressure liquid chromatography analysis of lipid oxidation products suggests that cellular lipoxygenases may also play a role at certain stages. In contrast, LDL isolated from atherosclerotic tissue is not enriched in protein oxidation products characteristic of free metal ions, which are the most widely studied in vitro model of LDL oxidation. These observations provide the first direct chemical evidence for reaction pathways that promote LDL oxidation in human atherosclerosis.
氧化损伤的低密度脂蛋白（LDL）可能在动脉粥样硬化性血管疾病的发病机制中起关键作用。体外有几种途径可促进LDL氧化，但生理相关机制难以确定。对特定反应途径产生的稳定化合物的检测为了解人类动脉壁氧化损伤机制提供了初步见解。对从动脉粥样硬化组织中分离出的蛋白质氧化产物进行质谱分析表明，酪氨酸自由基、活性氮中间体和次氯酸参与了体内LDL氧化和病变形成。次氯酸仅由吞噬酶髓过氧化物酶产生，该酶也可产生酪氨酸自由基和活性氮中间体。脂质氧化产物的手性相高压液相色谱分析表明，细胞脂氧合酶在某些阶段可能也起作用。相比之下，从动脉粥样硬化组织中分离出的LDL在游离金属离子特征性的蛋白质氧化产物中并不富集，而游离金属离子是体外研究最广泛的LDL氧化模型。这些观察结果为人类动脉粥样硬化中促进LDL氧化反应途径提供了首个直接化学证据。
