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 w hether lysophosphatidylcholine (lyso-PC), a prominent component of oxi datively modified LDL, induces migration of human coronary artery smoo th muscle cells (SMCs) and, if so, to clarify the mechanism, and (2) t o investigate the possible interactions of lyse-PC and platelet-derive d growth factor (PDGF)-BB, endothelin-1 (ET-1), adrenomedullin (AM), o r vitamin E on SMC migration by the Boyden's chamber method. Methods a nd Results-Lyse-PC induced SMC migration in a concentration-dependent manner between 10(-6) and 5X10(-5) mol/L. By contrast, phosphatidylcho line was without significant activity, and lysophosphatidylinositol an d lysophosphatidylserine were much less effective than lyse-PC. Lyse-P C increased basic fibroblast growth factor (bFGF) production in a conc entration-dependent manner between 10(-6) and 5X10-5 mol/L in these ce lls, Furthermore, lyse-PC-induced SMC migration was inhibited by neutr alizing antibody to bFGF but not by neutralizing antibody to transform ing 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 induce s human coronary artery SMC migration at least in part through release of endogenous bFGF and (2) this lyse-PC-induced migration can be furt her induced by PDGF-BB and ET-1 and can be inhibited by human AM and v itamin E. Lyse-PC may recruit medial SMCs during the process of corona ry atherosclerosis in part by releasing bFGF in concert with PDGF-BB o r ET-1 in vascular tissues. This lyso-PC-induced SMC migration may be suppressed by AM and vitamin E under certain pathological conditions.