title: Possible involvement of minor lysophospholipids in the increase in plasma lysophosphatidic acid in acute coronary syndrome.
abstract: 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.
  
  
  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.
authors.affiliation: 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.).
authors.forename: Makoto
authors.initials: M
authors.lastname: Kurano
authors.affiliation: 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.).
authors.forename: Akiko
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: 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.).
authors.forename: Asuka
authors.initials: A
authors.lastname: Inoue
authors.affiliation: 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.).
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Tokuhara
authors.affiliation: 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.).
authors.forename: Kuniyuki
authors.initials: K
authors.lastname: Kano
authors.affiliation: 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.).
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: 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.).
authors.forename: Koji
authors.initials: K
authors.lastname: Igarashi
authors.affiliation: 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.).
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Ohkawa
authors.affiliation: 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.).
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: 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.).
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Dohi
authors.affiliation: 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.).
authors.forename: Katsumi
authors.initials: K
authors.lastname: Miyauchi
authors.affiliation: 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.).
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Daida
authors.affiliation: 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.).
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Tsukamoto
authors.affiliation: 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.).
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: 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.).
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.affiliation: 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.). yatoyuta-tky@umin.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D002853:Chromatography, Liquid; D017023:Coronary Angiography; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000097:blood; D015539:Platelet Activation; D011237:Predictive Value of Tests; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation; D000099189:Lysophospholipase D
chemical_list: D015415:Biomarkers; D008077:Lipoproteins, LDL; D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D000099189:Lysophospholipase D; C099252:oxidized low density lipoprotein; C032881:lysophosphatidic acid
keywords: autotaxin; coronary disease; lysophosphatidic acids; lysophospholipids; molecular species