title: Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch.
abstract: We developed a compliant tube-type flow-loading apparatus that allows simultaneous application of physiological levels of shear stress and cyclic stretch to cultured cells and examined gene responses to a combination of the two forces. Human umbilical vein endothelial cells were exposed to shear stress and/or cyclic stretch for 24h, and changes in the mRNA levels of endothelin-1 (ET-1), a potent vasoconstrictor, and endothelial nitric oxide synthase (eNOS), which catalyzes the production of a potent vasodilator, NO, were determined by reverse transcriptase/PCR. Cyclic stretch (10%, 1 Hz) alone increased ET-1 mRNA levels approximately 1.6-fold, but had no effect on eNOS mRNA levels. A shear stress of 7 dynes/cm(2) and 15 dynes/cm(2) alone decreased ET-1 mRNA levels to around 83% and 61%, respectively, of the basal level, but increased the eNOS mRNA level to around 2.2-fold and 3.2-fold, respectively. When cyclic stretch and shear stress were applied simultaneously, ET-1 mRNA levels did not change significantly, but the eNOS mRNA level increased to a level equivalent to the increase in response to shear stress alone. These results indicate that the response of endothelial genes to shear stress or cyclic stretch depends on whether the two forces are applied separately or together.
authors.affiliation: Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Toda
authors.forename: Kimiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Shimizu
authors.forename: Syotaro
authors.initials: S
authors.lastname: Obi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kumagaya
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.forename: Akira
authors.initials: A
authors.lastname: Kamiya
authors.forename: Joji
authors.initials: J
authors.lastname: Ando
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D019332:Endothelin-1 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012828:Silicones; D013314:Stress, Mechanical
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger; D012828:Silicones; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III