The significance of lysophosphatidic acid in vascular biology and application of its measurement into laboratory medicine

本课题主要研究LPA在血管生物学中的意义以及LPA测量的临床应用。LPA受体，即LPAx在血小板和血管内皮细胞中的信号转导机制的阐明[j]。测定LPA和溶酶pld /autotaxin的临床应用确定测定LPA的血浆制备方法，设定血浆LPA的参考范围。然而，LPA浓度在刚孵育时急剧升高，而血清溶酶pld活性相对稳定。从运行内、运行间精密度、干扰、检出限、线性等方面分析，认为溶酶pld法可应用于临床实验室检测。健康女性血清溶酶pld活性（3.84±0.62 nmol/ml/min）显著高于男性（3.24±0.54 nmol/ml/min）。我们认为溶酶pld分析方法在实验室检测中是有前景的。LPA在血液中的代谢LPA在血液中的代谢是动态的。血浆LPA水平由LPC的溶酶pld产生和脂质磷酸酶的降解来平衡。此外，LPAx和脂质磷酸磷酸酶在靶细胞上的相对表达量可以确定LPA的生物学活性。分析溶酶pld /ATX和LPAx在各种细胞上的表达，这主要是在造血细胞上进行的。lysoPLD/ATX的表达似乎在造血分化过程中有所不同。慢性肝病患者血浆/血清LPA和溶酶pld测定的意义

In this research project, the significance of LPA in vascular biology and clinical application of the measurement of LPA have been pursued, as follows.1.The elucidation of signal transduction mechanisms of LPA receptor, i.e., LPAx, in platelets and vascular endothelial cells2.Clinical application of the measurement of LPA and lysoPLD/autotaxinThe plasma preparation method for LPA measurement was determined, and the reference range for plasma LPA was set. However, the concentration of LPA increased dramatically just under incubation while the serum lysoPLD activity was relatively stable. Based on the results on within-run and between-run precision, interference, detection limit, and linearity, it was considered that the lysoPLD assay can be applied to clinical laboratory testing. The serum lysoPLD activity in healthy female subjects (3.84 ± 0.62 nmol/ml/min) was significantly higher than that in the male subjects (3.24 ± 0.54 nmol/ml/min). We feel the lysoPLD assay method seems to be promising for laboratory testing.3.LPA metabolism in the bloodThe LPA metabolism is dynamic in the blood steam. The plasma LPA levels are balanced by its production by lysoPLD from LPC and degradation by lipid phosphate phosphatase. Furthermore, the biological activities of LPA may be determined by relative expression of LPAx and lipid phosphate phosphatase on target cells.4.The analysis of lysoPLD/ATX and LPAx expression on various cellsThis has been performed mainly on hematopoietic cells. The expression of lysoPLD/ATX seems to vary during hematopoietic differentiation.5.The significance of measurement of LPA and lysoPLD in the plasma/serum samples from chronic liver diseases