Endothelial gene expression in regions of defined shear exposure in the porcine iliac arteries.
Endothelial gene expression in regions of defined shear exposure in the porcine iliac arteries.
复制标题
猪髂动脉中特定剪切暴露区域的内皮基因表达。
DOI:
10.1007/s10439-010-0030-6
复制
发表时间:
2010
影响因子:
3.8
通讯作者:
Friedman,MortonH
中科院分区:
文献类型:
--
作者:
LaMack,JeffreyA;Himburg,HeatherA;Zhang,Ji;Friedman,MortonH
The effect of hemodynamic shear stress on endothelial gene expression was investigated in the porcine iliac arteries. A novel statistical approach was applied to computational fluid dynamics simulations of the iliac artery flow field to identify three anatomical regions likely to experience high, medium, and low levels of time average shear stress magnitude. Subsequently, endothelial cell mRNA was collected from these regions in the iliac arteries of six swine and analyzed by DNA microarray. Gene set enrichment analysis demonstrated a strong tendency for genes upregulated or downregulated in one of the extreme shear environments (low or high, relative to medium) to be regulated in the same direction in the other extreme shear environment. This tendency was confirmed for specific genes by real-time quantitative PCR. Specifically, β-catenin, c-jun, VCAM-1, and MCP-1 were all upregulated in low and high shear stress regions relative to the medium shear stress region. eNOS expression was not significantly different in any of the regions. These results are consistent with the notion that endothelial cells chronically exposed to abnormally low or high shear levelsin vivoexhibit similar genetic responses. Alternative explanations of this outcome are proposed, and its implications for the role of shear stress in atherogenesis are examined.