From the First Department of Internal Medicine, Osaka City University
Medical School, Japan.
Correspondence to Masakazu Kohno, MD, The First Department of Internal Medicine, Osaka City University Medical School, 1–5-7 Asahi-machi, Abeno-ku, Osaka 545, Japan.
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 lyso-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—Lyso-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 lyso-PC. Lyso-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, lyso-PC–induced SMC migration was inhibited by
neutralizing antibody to bFGF but not by neutralizing antibody to
transforming growth factor-ß1. Lyso-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) lyso-PC induces human
coronary artery SMC migration at least in part through release
of endogenous bFGF and (2) this lyso-PC–induced migration
can be further induced by PDGF-BB and ET-1 and can be inhibited by
human AM and vitamin E. Lyso-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.
© 1998 American Heart Association, Inc.
Basic Science Reports
Induction by Lysophosphatidylcholine, a Major Phospholipid Component of Atherogenic Lipoproteins, of Human Coronary Artery Smooth Muscle Cell Migration
Key Words: lysophosphatidylcholine • growth substances • adrenomedullin • endothelin • migration • cells
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