可能的小溶血磷脂参与急性冠状动脉综合征中血浆溶血磷脂酸的增加。
Possible involvement of minor lysophospholipids in the increase in plasma lysophosphatidic acid in acute coronary syndrome.
机构信息
From the Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan (M.K., A.S., H.I., Y.Y.); Core Research for Evolutional Science and Technology (CREST) (M.K., H.I., J.A., Y.Y.) and Precursory Research for Embryonic Science and Technology (PRESTO) (A.I.), Japan Science and Technology Agency (JST), Saitama, Japan; Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan (A.I., K.K., H.M., J.A.); Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan (Y.T., R.O., K.N., H.I., Y.Y.); Laboratory of Pathology, Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Kagawa, Japan (Y.T.); Bioscience Division, Reagent Development Department, AIA Research Group, TOSOH Corporation, Kanagawa, Japan (K.I.); Department of Cardiovascular Medicine, Juntendo University School of Medicine, Tokyo, Japan (T.D., K.M., H.D.); and Department of Metabolism, Diabetes and Nephrology, Preparatory Office for Aizu Medical Center, Fukushima Medical University, Fukushima, Japan (K.T.).
出版信息
Arterioscler Thromb Vasc Biol. 2015 Feb;35(2):463-70. doi: 10.1161/ATVBAHA.114.304748. Epub 2014 Nov 25.
OBJECTIVE
Lysophosphatidic acids (LPA) have important roles in the field of vascular biology and are derived mainly from lysophosphatidylcholine via autotaxin. However, in our previous study, only the plasma LPA levels, and not the serum autotaxin levels, increased in patients with acute coronary syndrome (ACS). The aim of this study was to elucidate the pathway by which LPA is increased in patients with ACS.
APPROACH AND RESULTS
We measured the plasma lysophospholipids species in 141 consecutive patients undergoing coronary angiography (ACS, n=38; stable angina pectoris, n=71; angiographically normal coronary arteries, n=32) using a liquid chromatography-tandem mass spectrometry analysis. Among the ACS subjects, notable increases in the 22:6 LPA, 18:2 LPA, and 20:4 LPA levels were observed. The in vitro experiments revealed that serum incubation mainly increased the 18:2 LPA level, whereas platelet activation increased the 20:4 LPA level. Minor lysophospholipids other than LPA were also elevated in ACS subjects and were well correlated with the corresponding LPA species, including 22:6 LPA. A multiple regression analysis also revealed that lysophosphatidylinositol, lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidylglycerol were independent explanatory variables for several LPA species.
CONCLUSIONS
Specific LPA species, especially long-chain unsaturated LPA, were elevated in ACS patients, along with the corresponding minor lysophospholipids. The elevation of these LPA species might be mainly caused by presently unidentified LPA-producing pathway(s). Minor lysophospholipids might be involved in the generation of LPA, especially 22:6 LPA, and in the pathogenesis of ACS.
目的
溶血磷脂酸（LPA）在血管生物学领域具有重要作用，主要来源于自分泌酶作用下的溶血磷脂酰胆碱。然而，在我们之前的研究中，只有急性冠脉综合征（ACS）患者的血浆 LPA 水平而不是血清自分泌酶水平升高。本研究旨在阐明 ACS 患者 LPA 升高的途径。
方法和结果
我们使用液相色谱-串联质谱分析方法测量了 141 例连续接受冠状动脉造影的患者的血浆溶血磷脂种类（ACS，n=38；稳定型心绞痛，n=71；血管造影正常的冠状动脉，n=32）。在 ACS 患者中，观察到 22:6 LPA、18:2 LPA 和 20:4 LPA 水平显著升高。体外实验表明，血清孵育主要增加 18:2 LPA 水平，而血小板激活增加 20:4 LPA 水平。ACS 患者中除 LPA 以外的其他溶血磷脂也升高，与相应的 LPA 种类（包括 22:6 LPA）高度相关。多元回归分析还表明，溶血磷脂酰肌醇、溶血磷脂酰胆碱、溶血磷脂酰乙醇胺和溶血磷脂酰甘油是几种 LPA 种类的独立解释变量。
结论
特定的 LPA 种类，特别是长链不饱和 LPA，在 ACS 患者中升高，同时伴有相应的小溶血磷脂。这些 LPA 种类的升高可能主要由目前尚未确定的 LPA 产生途径引起。小溶血磷脂可能参与 LPA 的生成，特别是 22:6 LPA，以及 ACS 的发病机制。
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