Shear Stress Inhibits Smooth Muscle Cell–Induced Inflammatory Gene Expression in Endothelial Cells: Role of NF-κB
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,...
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Published in | Arteriosclerosis, thrombosis, and vascular biology Vol. 25; no. 5; pp. 963 - 969 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Heart Association, Inc
01.05.2005
Hagerstown, MD Lippincott |
Subjects | |
Online Access | Get full text |
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Summary: | 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/cm) 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. |
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ISSN: | 1079-5642 1524-4636 |
DOI: | 10.1161/01.ATV.0000159703.43374.19 |