Miller Yury I, Chang Mi-Kyung, Binder Christoph J, Shaw Peter X, Witztum Joseph L
Department of Medicine, University of California, San Diego, La Jolla, California 92093-0682, USA.
Curr Opin Lipidol. 2003 Oct;14(5):437-45. doi: 10.1097/00041433-200310000-00004.
Atherosclerosis is now recognized as a chronic inflammatory disease. This review discusses recent literature reporting that innate immune receptors bind oxidatively modified LDL and its many oxidized moieties and consequently modulate the atherogenic process. These innate pattern recognition receptors are known to play a central role in pro-inflammatory responses to bacteria by binding pathogen-associated molecular patterns. It is hypothesized that oxidized LDL exposes similar molecular patterns recognized by receptors of innate immunity.
Minimally modified LDL and its oxidized phospholipids have been found to bind to CD14 or activate Toll-like receptors on macrophages. In turn, various biological activities have been induced, including the stimulation of cytoskeletal rearrangements that alter phagocytic activity and the stimulation of cytokine secretion, such as IL-8. These findings link modified LDL with innate pattern recognition receptors, such as those involved in the lipopolysaccharide signaling pathway. Human epidemiological studies support the involvement of CD14 and TLR4 in cardiovascular diseases. Oxidized LDL has also been demonstrated to bind to C-reactive protein, an opsonic molecule activating classic complement pathway and Fcgamma receptor endocytosis. These data suggest that C-reactive protein may not only be a strong predictor of clinical disease, but may also play a role in atherogenesis. Recent data on other innate immune receptors are discussed in the context of their potential interactions with oxidized LDL and atherogenesis.
Recent findings suggest that oxidized forms of LDL interact with innate immune receptors. Further studies are needed to identify the role of these interactions in inflammation and atherosclerosis.
动脉粥样硬化现已被公认为一种慢性炎症性疾病。本综述讨论了近期文献报道，即天然免疫受体可结合氧化修饰的低密度脂蛋白（LDL）及其多种氧化部分，从而调节动脉粥样硬化进程。已知这些天然模式识别受体通过结合病原体相关分子模式在对细菌的促炎反应中发挥核心作用。据推测，氧化LDL暴露了被天然免疫受体识别的类似分子模式。
已发现轻度修饰的LDL及其氧化磷脂可与CD14结合或激活巨噬细胞上的Toll样受体。进而诱导了各种生物学活性，包括刺激细胞骨架重排从而改变吞噬活性以及刺激细胞因子分泌，如白细胞介素-8。这些发现将修饰的LDL与天然模式识别受体联系起来，例如那些参与脂多糖信号通路的受体。人类流行病学研究支持CD14和TLR4参与心血管疾病。氧化LDL还被证明可与C反应蛋白结合，C反应蛋白是一种可激活经典补体途径和Fcγ受体胞吞作用的调理分子。这些数据表明，C反应蛋白不仅可能是临床疾病的有力预测指标，还可能在动脉粥样硬化形成中发挥作用。本文还在其他天然免疫受体与氧化LDL及动脉粥样硬化形成的潜在相互作用背景下讨论了近期相关数据。
近期研究发现表明，LDL的氧化形式与天然免疫受体相互作用。需要进一步研究来确定这些相互作用在炎症和动脉粥样硬化中的作用。
