Pulsatile Atheroprone Shear Stress Affects the Expression of Transient Receptor Potential Channels in Human Endothelial Cells
Pulsatile Atheroprone Shear Stress Affects the Expression of Transient Receptor Potential Channels in Human Endothelial Cells
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DOI：
10.1161/hypertensionaha.111.183608
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发表时间：
2012-06-01
期刊：
影响因子：
8.3
通讯作者：
Tepel, Martin
中科院分区：
文献类型：
--
作者：
Thilo, Florian;Vorderwuelbecke, Bernd J.;Tepel, Martin
该研究的目的是评估脉动动脉粥样硬化酮剪切应力是否调节瞬时受体电位（TRP）通道，TRPC 3，TRPC 6，TRPM 7和TRPV 1 mRNA在人脐血管内皮细胞中的表达。将培养的血管内皮细胞暴露于确定的剪切应力，产生恒定的层流（产生6达因/cm（2）的剪切应力），层流脉动动脉粥样硬化保护流（平均剪切应力为20达因/厘米（2）），或层流动脉粥样硬化酮双向流动（平均剪切应力为0达因/cm（2））差异诱导TRPC 6和TRPV 1 mRNA，如通过定量实时RT-PCR测量的，并标准化为GAPDH表达。因此，TRPC 6和TRPV 1 mRNA的表达显着增加后，24小时暴露于atheroprone流量曲线相比，动脉粥样硬化保护的流量曲线。此外，转录因子GATA 1和GATA 4的表达与TRPC 6 mRNA的表达显著相关。相反，在恒定层流24小时后，TRPC 6和TRPV 1 mRNA的表达没有变化，而TRPC 3和TRPM 7的表达在暴露于剪切应力的内皮细胞中比在静态条件下生长的内皮细胞显著更高。TRPC 6和肿瘤坏死因子-α mRNA在人血管组织中的表达存在显著相关性。无流动和动脉粥样硬化流动条件的特征同样是肿瘤坏死因子-α表达的增加;然而，正如我们研究中观察到的那样，在动脉粥样硬化流动条件下，TRPV 1和TRPC 6的增加可能会进一步加剧炎症相关的内皮细胞反应。（高血压。2012; 59：1232-1240）。
The goal of the study was to assess whether pulsatile atheroprone shear stress modulates the expression of transient receptor potential (TRP) channels, TRPC3, TRPC6, TRPM7, and TRPV1 mRNA, in human umbilical vascular endothelial cells. Exposure of cultured vascular endothelial cells to defined shear stress, producing a constant laminar flow (generating a shear stress of 6 dyne/cm(2)), laminar pulsatile atheroprotective flow (with a mean shear stress of 20 dyne/cm(2)), or laminar atheroprone bidirectional flow (with a mean shear stress of 0 dyne/cm(2)) differentially induced TRPC6 and TRPV1 mRNA as measured by quantitative real-time RT-PCR and normalized to GAPDH expression. Thereby, TRPC6 and TRPV1 mRNA expressions were significantly increased after 24 hours of exposure to an atheroprone flow profile compared with an atheroprotective flow profile. Furthermore, the expression of transcription factors GATA1 and GATA4 was significantly correlated with the expression of TRPC6 mRNA. In contrast, after 24 hours of constant laminar flow, the expression of TRPC6 and TRPV1 mRNA was unchanged, whereas the expression of TRPC3 and TRPM7 was significantly higher in endothelial cells exposed to shear stress in comparison with endothelial cells grown under static conditions. There was a significant association between the expression of TRPC6 and tumor necrosis factor-alpha mRNA in human vascular tissue. No-flow and atheroprone flow conditions are equally characterized by an increase in the expression of tumor necrosis factor-alpha; however, inflammation-associated endothelial cell reactions may be further aggravated at atheroprone flow conditions by the increase of TRPV1 and TRPC6, as observed in our study. (Hypertension. 2012; 59: 1232-1240.)