N-3 long-chain polyunsaturated fatty acids inhibit smooth muscle cell migration by modulating urokinase plasminogen activator receptor through MEK/ERK-dependent and -independent mechanisms

Claire Whyte, Frank Thies, Lise Peyrol, Denis Balcerzak

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Smooth muscle cell (SMC) migration is a major and complex feature of atherosclerosis and restenosis. N-3 long-chain polyunsaturated fatty acids (LCPUFAs) affect SMC migration; however, the mechanisms involved are unclear. This study investigated the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the MEK/ERK pathway and urokinase plasminogen activator receptor (uPAR) in relation to SMC migration.

Transwell migration assays revealed that both EPA and DHA decreased cell migration. Western blotting and real-time reverse transcription polymerase chain reaction showed that n-3 LCPUFAs decreased uPAR expression, but not urokinase plasminogen activator (uPA) expression, without changing plasmin and uPA activity. DHA also inhibited the activation of the MEK/ERK signaling pathway, whereas EPA switched the SMC phenotype from synthetic to contractile. siRNA technology targeting uPAR expression showed that decreased uPAR led to a significant decrease in migration, demonstrating the role of uPAR on SMC migration. We also showed that MEK/ERK pathway activation was involved in the regulation of uPAR gene expression in SMCs.

Our results suggest that n-3 LCPUFAs decrease SMC migration through the inhibition of uPAR expression, with DHA affecting its expression via the modulation of MEK/ERK signaling pathway, while EPA induces a change in SMC phenotype. This could represent another means by which to explain how n-3 LCPUFAs exert their preventive properties against atherosclerosis.
Original languageEnglish
Pages (from-to)1378-1383
Number of pages6
JournalThe Journal of Nutritional Biochemistry
Volume23
Issue number11
Early online date4 Jan 2012
DOIs
Publication statusPublished - Nov 2012

Keywords

  • docosahexaenoic acid
  • eicosapentaenoic acid
  • migration
  • aortic smooth muscle cells
  • urokinase plasminogen activator receptor
  • MEK/ERK

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