Cui Mei-Zhen
Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA.
Clin Lipidol. 2011 Aug;6(4):413-426. doi: 10.2217/clp.11.38.
Lysophosphatidic acid (LPA) has been found to accumulate in high concentrations in atherosclerotic lesions. LPA is a bioactive phospholipid produced by activated platelets and formed during the oxidation of LDL. Accumulating evidence suggests that this lipid mediator may serve as an important risk factor for development of atherosclerosis and thrombosis. The role of LPA in atherogenesis is supported by the evidence that LPA: stimulates endothelial cells to produce adhesion molecules and chemoattractants; induces smooth muscle cells to produce inflammatory cytokines; stimulates smooth muscle cell dedifferentiation, proliferation, and migration; increases monocyte migration and decreases monocyte-derived cell emigration from the vessel wall; induces hypertension and vascular neointimal formation in vivo; and promotes plaque progression in a mouse atherosclerosis model. The role of LPA in thrombogenesis is supported by the evidence that LPA markedly induces the aggregation of platelets and the expression of tissue factor, which is the principal initiator of blood coagulation. Recent experimental data indicate that LPA is produced by specific enzymes and that LPA binds to and activates multiple G-protein-coupled receptors, leading to intracellular signaling. Therapeutics targeting LPA biosynthesis, metabolism and signaling pathways could be viable for prevention and treatment of atherosclerosis and thrombosis.
溶血磷脂酸（LPA）已被发现在动脉粥样硬化病变中高浓度蓄积。LPA是一种由活化血小板产生并在低密度脂蛋白氧化过程中形成的生物活性磷脂。越来越多的证据表明，这种脂质介质可能是动脉粥样硬化和血栓形成发展的重要危险因素。LPA在动脉粥样硬化发生中的作用得到以下证据的支持：LPA刺激内皮细胞产生黏附分子和趋化因子；诱导平滑肌细胞产生炎性细胞因子；刺激平滑肌细胞去分化、增殖和迁移；增加单核细胞迁移并减少单核细胞衍生细胞从血管壁的迁出；在体内诱导高血压和血管内膜形成；并在小鼠动脉粥样硬化模型中促进斑块进展。LPA在血栓形成中的作用得到以下证据的支持：LPA显著诱导血小板聚集和组织因子表达，而组织因子是血液凝固的主要启动因子。最近的实验数据表明，LPA由特定酶产生，并且LPA与多种G蛋白偶联受体结合并激活，从而导致细胞内信号传导。针对LPA生物合成、代谢和信号通路的治疗方法可能对动脉粥样硬化和血栓形成的预防和治疗可行。
