Miller Yury I
Department of Medicine, University of California, San Diego, USA.
Future Cardiol. 2005 Nov;1(6):785-92. doi: 10.2217/14796678.1.6.785.
The oxidation hypothesis of atherosclerosis suggests that oxidative modification of low-density lipoprotein (LDL) is a prerequisite for LDL atherogenicity. Recent studies demonstrate that upon oxidative modification, LDL becomes enriched with pathogen-associated molecular patterns recognized by natural (inborn) antibodies and innate immune receptors. This review focuses on recent findings showing that Toll-like receptors (TLRs)--which sense microbial pathogens and initiate immediate inflammatory responses--are potentially involved in the pathogenesis of atherosclerosis. In addition to the data that bacterial agonists of TLR4 and TLR2 accelerate atherosclerosis, new evidence suggests that minimally oxidized LDL and specific oxidized phospholipids signal via TLRs to induce cytoskeletal changes and inflammatory cytokine secretion by macrophages and endothelial cells. Identifying the signaling mechanisms by which oxidized LDL induces chronic inflammation in atherosclerotic lesions may lead to novel therapeutic targets for the treatment of atherosclerotic cardiovascular disease.
动脉粥样硬化的氧化假说表明，低密度脂蛋白（LDL）的氧化修饰是LDL致动脉粥样硬化性的先决条件。最近的研究表明，在氧化修饰后，LDL富含天然（先天）抗体和先天免疫受体所识别的病原体相关分子模式。本综述重点关注最近的研究结果，这些结果表明，可感知微生物病原体并引发即时炎症反应的Toll样受体（TLR）可能参与动脉粥样硬化的发病机制。除了TLR4和TLR2的细菌激动剂可加速动脉粥样硬化的数据外，新证据表明，轻度氧化的LDL和特定的氧化磷脂通过TLR发出信号，以诱导巨噬细胞和内皮细胞的细胞骨架变化和炎性细胞因子分泌。确定氧化LDL在动脉粥样硬化病变中诱导慢性炎症的信号传导机制，可能会为动脉粥样硬化性心血管疾病的治疗带来新的治疗靶点。
