Abstract
We investigate the role of shear stress in regulating the gene expression in endothelial cells (ECs) in response to tumor necrosis factor-α (TNF-α). ECs were kept in static condition or pre-exposed to a high level (HSS, 20 dynes/cm2) or a low level of shear stress (LSS, 0.5 dynes/cm2) for 24 h, and TNF-α was added under static condition for 4 h. In static ECs, DNA microarray showed that TNF-α caused a significant increase in expression of 102 genes and a significant decrease in expression of 12 genes. Pre-shearing of ECs decreased the TNF-α- responsiveness of many pro-inflammatory, pro-coagulant, proliferative, and pro-apoptotic genes, whereas it increased the responsiveness of some antioxidant, anti-coagulant, and anti-apoptotic genes. LSS showed less regulatory effects than HSS on EC gene expression in response to TNF-α. The microarray data were confirmed by reverse-transcription polymerase chain reaction for 64 selected genes. Pre-shearing of ECs at HSS significantly inhibited the TNF-α-induced p65 and p50 mRNA expressions and nuclear factor-κB (NF-κB)-DNA binding activity. Inhibition of NF-κB activity with the p65-antisense or lactacystin under static condition blocked the expression of most of the genes that are TNF-α-inducible and shear stress-down-regulated. Our findings suggest that laminar shear stress serves protective functions against atherogenesis.
Original language | English |
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Pages (from-to) | 481-502 |
Number of pages | 22 |
Journal | Journal of Biomedical Science |
Volume | 12 |
Issue number | 3 |
DOIs | |
Publication status | Published - May 1 2005 |
Externally published | Yes |
Keywords
- cDNA microarray
- Cytokine
- Endothelial cell
- Gene expression
- Shear stress
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Molecular Biology
- Clinical Biochemistry
- Cell Biology
- Biochemistry, medical
- Pharmacology (medical)