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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1617.)
© 2002 American Heart Association, Inc.

Vascular Biology

Lysophosphatidylcholine Stimulates Monocyte Chemoattractant Protein-1 Gene Expression in Rat Aortic Smooth Muscle Cells

James X. Rong; Joan W. Berman; Mark B. Taubman; Edward A. Fisher

From the Department of Medicine and The Zena and Michael A. Wiener Cardiovascular Institute (J.X.R., M.B.T., E.A.F.), Mount Sinai School of Medicine, New York, NY, and the Departments of Pathology and Microbiology and Immunology (J.W.B.), Albert Einstein College of Medicine, Bronx, NY.

Correspondence to Dr Edward A. Fisher, Box 1269, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029. E-mail edward.fisher{at}mssm.edu

Objective— Monocyte chemoattractant protein (MCP)-1 is a proatherogenic factor that is responsible for 60% of plaque macrophages in mouse models of atherosclerosis. We investigated whether lysophosphatidylcholine (LPC), enriched in oxidized low density lipoprotein, can modulate the expression of MCP-1 in arterial wall cells.

Methods and Results— LPC induced a 3-fold increase in MCP-1 mRNA in rat vascular smooth muscle cells (VSMCs) in a time- and dose-dependent manner. Nuclear runon analysis showed that this increase was attributable to increased MCP-1 gene transcription. There was a 2-fold increase in MCP-1 protein in the conditioned media of cells treated with LPC. LPC-associated increases of MCP-1 mRNA and protein were similar to those produced by platelet-derived growth factor-BB, a known inducer of MCP-1. Analyses of the MCP-1 promoter in transiently transfected VSMCs indicated an LPC-responsive element(s) between base pairs -146 and -261 (relative to transcription initiation). Further studies suggested that LPC-induced MCP-1 expression partially involves mitogen-activated protein kinase/extracellular signal–regulated kinase, a tyrosine kinase(s), and (to a lesser extent) protein kinase C but not the activation of the platelet-derived growth factor receptor.

Conclusions— LPC stimulates MCP-1 expression at the transcriptional level in VSMCs, suggesting a molecular mechanism by which LPC contributes to the atherogenicity of oxidized low density lipoprotein.

Key Words: lysophosphatidylcholine • monocyte chemoattractant protein-1 • smooth muscle cells • tyrosine kinase • mitogen-activated protein kinase/extracellular signal–regulated kinase

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