- 作者: Jeng-Jiann Chiu; Pei-Ling Lee; Shun-Fu Chang; Li-Jing Chen; Chih-I Lee; Kurt M. Lin; Shunichi Usami; Shu Chien
- 作者服務機構: a Division of Medical Engineering Research, National Health Research Institutes, Miaoli, 350, Taiwan, ROC; ; b Institute of Biomedical Engineering, National Yang-Ming University, Taipei, 112, Taiwan, ROC; ; c Departments of Bioengineering and Medicine and Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, CA92093-0427
- 中文摘要: --
- 英文摘要: 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.
- 中文關鍵字: --
- 英文關鍵字: cDNA microarray, cytokine, endothelial cell, gene expression, shear stress