Induction by lysophosphatidylcholine, a major phospholipid component of atherogenic lipoproteins, of human coronary artery smooth muscle cell migration

Background-The objectives of the present study were (1) to determine whether lysophosphatidylcholine (lyso-PC), a prominent component of oxidatively modified LDL, induces migration of human coronary artery smooth muscle cells (SMCs) and, if so, to clarify the mechanism, and (2) to investigate the possible interactions of lyse-PC and platelet-derived growth factor (PDGF)-BB, endothelin-1 (ET-1), adrenomedullin (AM), or vitamin E on SMC migration by the Boyden's chamber method. Methods and Results-Lyse-PC induced SMC migration in a concentration-dependent manner between 10(-6) and 5X10(-5) mol/L. By contrast, phosphatidylcholine was without significant activity, and lysophosphatidylinositol and lysophosphatidylserine were much less effective than lyse-PC. Lyse-PC increased basic fibroblast growth factor (bFGF) production in a concentration-dependent manner between 10(-6) and 5X10-5 mol/L in these cells, Furthermore, lyse-PC-induced SMC migration was inhibited by neutralizing antibody to bFGF but not by neutralizing antibody to transforming growth factor-beta(1). Lyse-PC-induced migration was significantly enhanced by PDGF-BB or ET-1 but was clearly inhibited by human AM and vitamin E, Conclusions-These results indicate that (1) lyse-PC induces human coronary artery SMC migration at least in part through release of endogenous bFGF and (2) this lyse-PC-induced migration can be further induced by PDGF-BB and ET-1 and can be inhibited by human AM and vitamin E. Lyse-PC may recruit medial SMCs during the process of coronary atherosclerosis in part by releasing bFGF in concert with PDGF-BB or ET-1 in vascular tissues. This lyso-PC-induced SMC migration may be suppressed by AM and vitamin E under certain pathological conditions.