title: Pulsatile atheroprone shear stress affects the expression of transient receptor potential channels in human endothelial cells.
abstract: 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.
authors.affiliation: Department of Nephrology, Charité Campus Benjamin Franklin, Berlin, Germany. Florian.Thilo@charite.de
authors.forename: Florian
authors.initials: F
authors.lastname: Thilo
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Vorderwülbecke
authors.forename: Alex
authors.initials: A
authors.lastname: Marki
authors.forename: Katharina
authors.initials: K
authors.lastname: Krueger
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Daniel
authors.initials: D
authors.lastname: Baumunk
authors.forename: Andreas
authors.initials: A
authors.lastname: Zakrzewicz
authors.forename: Martin
authors.initials: M
authors.lastname: Tepel
mesh_terms: D001158:Arteries / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011673:Pulsatile Flow / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism; D000074287:TRPC6 Cation Channel; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D050053:TRPM Cation Channels; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human