Department of Pathology, University of California-Los Angeles, MRL 4760, 675 Charles E. Young Dr. S., Los Angeles, CA 90095, USA.
Circ Res. 2012 Aug 31;111(6):778-99. doi: 10.1161/CIRCRESAHA.111.256859.
There is increasing clinical evidence that phospholipid oxidation products (Ox-PL) play a role in atherosclerosis. This review focuses on the mechanisms by which Ox-PL interact with endothelial cells, monocyte/macrophages, platelets, smooth muscle cells, and HDL to promote atherogenesis. In the past few years major progress has been made in identifying these mechanisms. It has been recognized that Ox-PL promote phenotypic changes in these cell types that have long-term consequences for the vessel wall. Individual Ox-PL responsible for specific cellular effects have been identified. A model of the configuration of bioactive truncated Ox-PL within membranes has been developed that demonstrates that the oxidized fatty acid moiety protrudes into the aqueous phase, rendering it accessible for receptor recognition. Receptors and signaling pathways for individual Ox-PL species are now determined and receptor independent signaling pathways identified. The effects of Ox-PL are mediated both by gene regulation and transcription independent processes. It has now become apparent that Ox-PL affects multiple genes and pathways, some of which are proatherogenic and some are protective. However, at concentrations that are likely present in the vessel wall in atherosclerotic lesions, the effects promote atherogenesis. There have also been new insights on enzymes that metabolize Ox-PL and the significance of these enzymes for atherosclerosis. With the knowledge we now have of the regulation and effects of Ox-PL in different vascular cell types, it should be possible to design experiments to test the role of specific Ox-PL on the development of atherosclerosis.
越来越多的临床证据表明，磷脂氧化产物（Ox-PL）在动脉粥样硬化中起作用。这篇综述重点介绍了 Ox-PL 与内皮细胞、单核细胞/巨噬细胞、血小板、平滑肌细胞和 HDL 相互作用促进动脉粥样硬化形成的机制。在过去的几年中，在确定这些机制方面取得了重大进展。人们已经认识到，Ox-PL 促进这些细胞类型的表型变化，对血管壁产生长期影响。已经确定了负责特定细胞效应的个别 Ox-PL。已经开发出一种在膜内具有生物活性截断 Ox-PL 的构象模型，该模型表明氧化脂肪酸部分突出到水相，使其可用于受体识别。现在已经确定了个别 Ox-PL 物种的受体和信号转导途径，以及受体非依赖性信号转导途径。Ox-PL 的作用通过基因调控和转录非依赖性过程来介导。现在已经很明显，Ox-PL 影响多个基因和途径，其中一些是促动脉粥样硬化的，而另一些是保护的。然而，在动脉粥样硬化病变中血管壁中可能存在的浓度下，这些作用促进了动脉粥样硬化的形成。关于代谢 Ox-PL 的酶以及这些酶对动脉粥样硬化的意义也有了新的认识。鉴于我们现在对不同血管细胞类型中 Ox-PL 的调节和作用的了解，应该有可能设计实验来测试特定 Ox-PL 在动脉粥样硬化发展中的作用。
