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

本研究主要围绕LPA在血管生物学中的意义及LPA测定的临床应用进行了如下研究：1.阐明LPA受体的信号转导机制，即：2. LPA和lysoPLD/autotaxin测定的临床应用确定了LPA测定的血浆制备方法，并设定了血浆LPA的参考范围。而血清lysoPLD活性相对稳定，但在孵育过程中LPA浓度急剧升高。基于批内和批间精密度、干扰、检测限和线性的结果，认为lysoPLD测定法可应用于临床实验室检测。健康女性血清lysoPLD活性（3.84 ± 0.62 nmol/ml/min）明显高于男性（3.24 ± 0.54 nmol/ml/min）。我们认为lysoPLD检测方法在实验室检测中是有希望的。3. LPA在血液中的代谢LPA在血液中的代谢是动态的。血浆LPA水平通过其由LPC的lysoPLD产生和由脂质磷酸磷酸酶降解来平衡。LPA的生物学活性可以通过LPAx和LPAx在靶细胞上的相对表达来确定。4.各种细胞上lysoPLD/ATX和LPAx表达的分析这主要是在造血细胞上进行的。lysoPLD/ATX在造血细胞分化过程中的表达可能发生变化。5.慢性肝病患者血浆和血清中LPA和lysoPLD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