Frequency-dependent response of the vascular endothelium to pulsatile shear stress
Frequency-dependent response of the vascular endothelium to pulsatile shear stress
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DOI：
10.1152/ajpheart.01087.2006
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发表时间：
2007-07-01
影响因子：
4.8
通讯作者：
Friedman, Morton H.
中科院分区：
文献类型：
--
作者：
Himburg, Heather A.;Dowd, Scot E.;Friedman, Morton H.
由于动脉树中存在复杂的血流模式，血管壁的某些区域会经历剪切应力的波动，该波动主要由高于心率的谐波频率决定 (11)。为了评估频率变化是否影响内皮基因表达，将培养的猪主动脉内皮暴露于三种正弦波形（1、2和3 Hz；振幅= 15 dyn/cm(2)）和一种生理波形的基因表达模式与稳定流引起的表达谱进行比较。在每个频率（包括稳定流）下，使用三个水平的平均剪切应力（0、7.5 和 15 dyn/cm(2)）。剪切暴露 24 小时后，提取 RNA 用于针对 10,665 个野猪寡核苷酸进行微阵列分析。双向方差分析确定了 232 个基因，这些基因的转录受到频率的差异调节，而平均剪切显着影响了大约 3,000 个基因的表达。单向方差分析表明，随着平均剪切应力的降低，频率依赖性基因的数量增加。在 1 Hz 时，相对于稳定流，一些炎症转录本被抑制，包括 VCAM 和 IL-8，而一些动脉粥样硬化转录本被诱导。 1 Hz 时的抗炎反应在 2 Hz 时逆转。较高频率引起的促炎反应在反向和振荡剪切下最为明显。这项研究表明，受到剪切逆转和超过正常心率的主导频率影响的动脉区域发生动脉粥样硬化病变的风险更大。
As a result of the complex blood flow patterns that occur in the arterial tree, certain regions of the vessel wall experience fluctuations in shear stress that are dominated by harmonic frequencies higher than the heart rate (11). To assess whether variations in frequency affect endothelial gene expression, the gene expression patterns of cultured porcine aortic endothelium exposed to three sinusoidal waveforms (1, 2, and 3 Hz; amplitude = 15 dyn/cm(2)) and one physiological waveform were compared with the expression profiles elicited by steady flow. At each frequency, including steady flow, three levels of mean shear stress (0, 7.5, and 15 dyn/cm(2)) were used. After 24 h shear exposure, RNA was extracted for microarray analysis against 10,665 Sus scrofa oligonucleotides. A two-way ANOVA identified 232 genes of which their transcription was differentially modulated by frequency, while mean shear significantly affected the expression of similar to 3,000 genes. One-way ANOVAs showed that the number of frequency-dependent genes increased as the mean shear stress was reduced. At 1 Hz, several inflammatory transcripts were repressed relative to steady flow, including VCAM and IL-8, whereas several atheroprotective transcripts were induced. The anti-inflammatory response at 1 Hz was reversed at 2 Hz. The proinflammatory response evoked by the higher frequency was most pronounced under reversing and oscillatory shear. This study suggests that arterial regions subject to both shear reversal and dominant frequencies that exceed the normal heart rate are at greater risk for atherosclerotic lesion development.