Possible Involvement of Minor Lysophospholipids in the Increase in Plasma Lysophosphatidic Acid in Acute Coronary Syndrome

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.