The bioactive lipid lysophosphatidic acid (LPA) is emerging as an important mediator of inflammation in cardiovascular diseases. Produced in large part by the secreted lysophospholipase D autotaxin (ATX), LPA acts on a series of G protein-coupled receptors and may have action on atypical receptors such as RAGE to exert potent effects on vascular cells, including the promotion of foam cell formation and phenotypic modulation of smooth muscle cells. The signaling effects of LPA can be terminated by integral membrane lipid phosphate phosphatases (LPP) that hydrolyze the lipid to receptor inactive products. Human genetic variants in PLPP3, that predict lower levels of LPP3, associate with risk for premature coronary artery disease, and reductions of LPP3 expression in mice promote the development of experimental atherosclerosis and enhance inflammation in the atherosclerotic lesions. Recent evidence also supports a role for ATX, and potentially LPP3, in calcific aortic stenosis. In summary, LPA may be a relevant inflammatory mediator in atherosclerotic cardiovascular disease and heightened LPA signaling may explain the cardiovascular disease risk effect of PLPP3 variants.

中文翻译：

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溶血磷脂酸信号在血管发育和疾病中的作用。

生物活性脂质溶血磷脂酸 (LPA) 正在成为心血管疾病炎症的重要介质。LPA 主要由分泌的溶血磷脂酶 D 自分泌运动因子 (ATX) 产生，作用于一系列 G 蛋白偶联受体，并可能作用于非典型受体，例如 RAGE，从而对血管细胞产生强效作用，包括促进泡沫细胞形成和平滑肌细胞的表型调节。LPA 的信号传导作用可以被整合膜脂质磷酸酶 (LPP) 终止，LPP 将脂质水解为受体无活性产物。PLPP3 中的人类遗传变异，预测较低水平的 LPP3，与早发冠状动脉疾病的风险相关，小鼠中 LPP3 表达的减少促进实验性动脉粥样硬化的发展并增强动脉粥样硬化病变中的炎症。最近的证据还支持 ATX 和潜在的 LPP3 在钙化性主动脉瓣狭窄中的作用。总之，LPA 可能是动脉粥样硬化性心血管疾病的相关炎症介质，增强的 LPA 信号可能解释了 PLPP3 变体对心血管疾病的风险影响。