Pulsatile Atheroprone Shear Stress Affects the Expression of Transient Receptor Potential Channels in Human Endothelial Cells

被引:34
作者
Thilo, Florian [1 ]
Vorderwuelbecke, Bernd J. [2 ]
Marki, Alex [2 ]
Krueger, Katharina [1 ]
Liu, Ying [3 ,4 ,5 ]
Baumunk, Daniel [6 ]
Zakrzewicz, Andreas [2 ]
Tepel, Martin [3 ,4 ]
机构
[1] Charite Campus Benjamin Franklin, Dept Nephrol, Thielallee 71, D-14195 Berlin, Germany
[2] Charite Campus Benjamin Franklin, Shear Stress & Vasc Biol Res Grp, Inst Physiol, D-14195 Berlin, Germany
[3] Odense Univ Hosp, Inst Mol Med Cardiovasc & Renal Res, Inst Clin Res, DK-5000 Odense, Denmark
[4] Univ Southern Denmark, Odense, Denmark
[5] Tongji Univ, Dept Urol, Peoples Hosp 10, Shanghai 200092, Peoples R China
[6] Univ Magdeburg, Dept Urol, D-39106 Magdeburg, Germany
关键词
TRP channels; mRNA expression; shear stress; endothelial cells; VASCULAR ENDOTHELIUM; SMOOTH-MUSCLE; FLOW; ACTIVATION; PHENOTYPES; RESPONSES;
D O I
10.1161/HYPERTENSIONAHA.111.183608
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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.)
引用
收藏
页码:1232 / 1240
页数:9
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