Possible involvement of minor lysophospholipids in the increase in plasma lysophosphatidic acid in acute coronary syndrome

Makoto Kurano; Akiko Suzuki; Asuka Inoue; Yasunori Tokuhara; Kuniyuki Kano; Hirotaka Matsumoto; Koji Igarashi; Ryunosuke Ohkawa; Kazuhiro Nakamura; Tomotaka Dohi; Katsumi Miyauchi; Hiroyuki Daida; Kazuhisa Tsukamoto; Hitoshi Ikeda; Junken Aoki; Yutaka Yatomi

doi:10.1161/ATVBAHA.114.304748

Possible involvement of minor lysophospholipids in the increase in plasma lysophosphatidic acid in acute coronary syndrome

Arterioscler Thromb Vasc Biol. 2015 Feb;35(2):463-70. doi: 10.1161/ATVBAHA.114.304748. Epub 2014 Nov 25.

Authors

Makoto Kurano¹, Akiko Suzuki¹, Asuka Inoue¹, Yasunori Tokuhara¹, Kuniyuki Kano¹, Hirotaka Matsumoto¹, Koji Igarashi¹, Ryunosuke Ohkawa¹, Kazuhiro Nakamura¹, Tomotaka Dohi¹, Katsumi Miyauchi¹, Hiroyuki Daida¹, Kazuhisa Tsukamoto¹, Hitoshi Ikeda¹, Junken Aoki¹, Yutaka Yatomi²

Affiliations

¹ 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.).
² 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.

PMID: 25425621
DOI: 10.1161/ATVBAHA.114.304748

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.

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.

Keywords: autotaxin; coronary disease; lysophosphatidic acids; lysophospholipids; molecular species.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Coronary Syndrome / blood*
Acute Coronary Syndrome / diagnosis
Biomarkers / blood
Blood Platelets / metabolism
Chromatography, Liquid
Coronary Angiography
Female
Humans
Lipoproteins, LDL / blood
Lysophospholipids / blood*
Male
Phosphoric Diester Hydrolases / blood
Platelet Activation
Predictive Value of Tests
Tandem Mass Spectrometry
Up-Regulation

Substances

Biomarkers
Lipoproteins, LDL
Lysophospholipids
oxidized low density lipoprotein
Phosphoric Diester Hydrolases
alkylglycerophosphoethanolamine phosphodiesterase
lysophosphatidic acid