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

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1617-1623
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume22
Issue number10
DOIs
StatePublished - Oct 1 2002

Keywords

  • Lysophosphatidylcholine
  • Mitogen-activated protein kinase/extracellular signal-regulated kinase
  • Monocyte chemoattractant protein-1
  • Smooth muscle cells
  • Tyrosine kinase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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