Shear stress inhibits smooth muscle cell-induced inflammatory gene expression in endothelial cells: Role of NF-κB

Jeng Jiann Chiu, Li Jing Chen, Shun Fu Chang, Pei Ling Lee, Chih I. Lee, Min Chien Tsai, Ding Yu Lee, Hsing Pang Hsieh, Shunichi Usami, Shu Chien

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Objectives - Vascular endothelial cells (ECs) are influenced by shear stress and neighboring smooth muscle cells (SMCs). We investigated the inflammation-relevant gene expression in EC/SMC cocultures under static condition and in response to shear stress. Materials and Methods - Under static condition, DNA microarrays and reverse-transcription polymerase chain reaction identified 23 inflammation-relevant genes in ECs whose expression was significantly affected by coculture with SMCs, with 18 upregulated and 5 downregulated. Application of shear stress (12 dynes/cm2) to the EC side of the coculture for 6 hours inhibited most of the proinflammatory gene expressions in ECs induced by coculture with SMCs. Inhibition of nuclear factor-κB (NF-κB) activation by the p65-antisense, lactacystin, and N-acetyl-cysteine blocked the coculture-induced EC expression of proinflammatory genes, indicating that the NF-κB binding sites in the promoters of these genes play a significant role in their expression as a result of coculture with SMCs. Chromatin immunoprecipitation assays demonstrated the in vivo regulation of NF-κB recruitment to selected target promoters. Shear stress inhibited the SMC coculture-induced NF-κB activation in ECs and monocytic THP-1 cell adhesion to ECs. Conclusions - Our findings suggest that shear stress plays an inhibitory role in the proinflammatory gene expression in ECs located in close proximity to SMCs.

Original languageEnglish
Pages (from-to)963-969
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume25
Issue number5
DOIs
Publication statusPublished - May 1 2005
Externally publishedYes

Keywords

  • cDNA microarray
  • Coculture
  • Endothelial cells
  • Shear stress
  • Smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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