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

Department of Nephrology, Charité Campus Benjamin Franklin, Berlin, Germany.
Hypertension (Impact Factor: 6.48). 05/2012; 59(6):1232-40. DOI: 10.1161/HYPERTENSIONAHA.111.183608
Source: PubMed


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-α mRNA in human vascular tissue. No-flow and atheroprone flow conditions are equally characterized by an increase in the expression of tumor necrosis factor-α; 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.

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Available from: Min Liu, Jan 13, 2016
    • "However, this report is the only one demonstrating the existence of TRPC5/6 heteromeric channels, while other studies excluded this sort of heteromultimerisation (see above and Hofmann et al. 2002; Goel et al. 2002; Strubing et al. 2003). Very recently, it was reported that atheroprone shear stress induced TRPC6 and TRPV1 mRNA expression in endothelial cells, but a putative role of TRPC6 in atherosclerosis remains elusive (Thilo et al. 2012). Smooth muscle cells provide not only structural integrity for the vessel but also precise regulation of vascular tone and blood pressure. "
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    ABSTRACT: TRPC6 is a non-selective cation channel 6 times more permeable to Ca2+ than to Na+. Channel homotetramers heterologously expressed have a characteristic doubly rectifying current-voltage relationship and are directly activated by the second messenger diacylglycerol (DAG). TRPC6 proteins are also regulated by specific tyrosine or serine phosphorylation and phosphoinositides. Given its specific expression pattern, TRPC6 is likely to play a number of physiological roles which are confirmed by the analysis of a Trpc6 −/− mouse model. In smooth muscle Na+ influx through TRPC6 channels and activation of voltage-gated Ca2+ channels by membrane depolarisation is the driving force for contraction. Permeability of pulmonary endothelial cells depends on TRPC6 and induces ischaemia–reperfusion oedema formation in the lungs. TRPC6 was also identified as an essential component of the slit diaphragm architecture of kidney podocytes and plays an important role in the protection of neurons after cerebral ischaemia. Other functions especially in immune and blood cells remain elusive. Recently identified TRPC6 blockers may be helpful for therapeutic approaches in diseases with highly activated TRPC6 channel activity.
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    • "In endothelial cells derived from the umbilical vein (HUVEC), two independent reports have shown that siRNAs transiently silencing TRPM7 stimulate cell proliferation [9], [10], a behaviour which is unique to HUVEC, because in various cell types silencing TRPM7 induces cell cycle arrest. In addition to the significant elevation of TRPM7 in the vasculature of MgL mice [4], the increase of TRPM7 transcript in HUVEC exposed to shear stress has been described [11]. "
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