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

本研究从以下几个方面探讨了LPA在血管生物学中的意义及其临床应用：1.阐明了LPA受体即LPAx在血小板和血管内皮细胞中的信号转导机制2.LPA和溶血磷脂酶D/自体的测定的临床应用确定了测定LPA的血浆制备方法，并设定了血浆LPA的参考范围。然而，LPA浓度仅在孵育时显著增加，而血清溶血磷脂酶D活性相对稳定。根据批内和批间精密度、干扰、检出限和线性的结果，认为溶血磷脂酶D法可用于临床实验室检测。健康女性血清溶血磷脂酶D活性(3.84±0.62nmol/ml/min)显著高于男性(3.24±0.54nmol/ml/min)。LPA在血液中的代谢在血液中的代谢是动态的。血浆LPA水平由LPC产生的溶菌PLD和脂磷酸盐磷酸酶降解所平衡。此外，LPA的生物学活性可能取决于LPAx和靶细胞上脂质磷酸酶的相对表达。4.不同细胞上LPAx和LPAx表达的分析这主要是在造血细胞上进行的。5.慢性肝病患者血浆/血清中LPA和LPLD检测的意义

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