Both plasma lysophosphatidic acid and serum autotaxin levels are increased in chronic hepatitis C

Both plasma lysophosphatidic acid and serum autotaxin levels are increased in chronic hepatitis C
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DOI:
10.1097/01.mcg.0000225642.90898.0e
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发表时间:
2007-07-01
影响因子:
2.9
通讯作者:
Yatomi, Yutaka
Yatomi, Yutaka
中科院分区:
医学3区
文献类型:
--
作者:
Watanabe, Naoko;Ikeda, Hitoshi;Yatomi, Yutaka

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目的:最近越来越多的证据表明,溶血磷脂酸(LPA)是一种脂质介质,大量存在于血液中,具有广泛的生物作用,包括调节肝细胞的增殖和收缩。虽然推测LPA可能在体内的病理生理过程中发挥作用,但在特定疾病下,不仅其作用,甚至其血药浓度的可能改变,基本上都是未知的。Autotaxin (ATX)最初被纯化为黑色素瘤细胞的自分泌运动因子,被发现是LPA合成的关键酶。我们测定了肝病患者血液中的LPA和ATX水平。方法:采用溶血磷脂酰胆碱底物测定胆碱法测定41例慢性丙型肝炎患者血清ATX活性,酶循环法测定LPA水平。结果:患者血清ATX活性和血浆LPA水平显著升高,且与血清透明质酸呈正相关,与血小板、白蛋白和凝血酶原时间呈负相关。血浆LPA水平与血清ATX活性密切相关。纤维化组织学分期与血清ATX活性和血浆LPA水平有显著相关性。结论:慢性丙型肝炎患者血清ATX活性和血浆LPA水平升高与肝纤维化有关。我们的研究可能提供了第一个证据,表明在特定疾病下血液中ATX和LPA均显着增加。
Objectives: Recent accumulating evidence indicates that lysophosphatidic acid (LPA) is a lipid mediator, abundantly present in blood, with a wide range of biologic actions including the regulation of proliferation and contraction in liver cells. Although it is speculated that LPA might play a role in pathophysiologic processes in vivo, not only its role but also even a possible alteration in its blood concentration under specific diseases is essentially unknown. Autotaxin (ATX), originally purified as an autocrine motility factor for melanoma cells, was revealed to be a key enzyme in LPA synthesis. We determined LPA and ATX levels in the blood of patients with liver disease.Methods: ATX activity was measured by determining choline with the substrate of lysophosphatidylcholine, and the LPA level by an enzymatic cycling method in 41 patients with chronic hepatitis C.Results: The serum ATX activity and plasma LPA level were significantly increased in patients, and were correlated positively with serum hyaluronic acid, and negatively with platelets, albumin, and prothrombin time. The plasma LPA level was strongly correlated with serum ATX activity. There were significant correlations between the histologic stage of fibrosis and both the serum ATX activity and plasma LPA level.Conclusions: The serum ATX activity and plasma LPA level are increased in chronic hepatitis C in association with liver fibrosis. Our study may provide the first evidence showing a significant increase of both ATX and LPA in the blood under a specific disease.