title: Cyclic stretch induces cyclooxygenase-2 gene expression in vascular endothelial cells via activation of nuclear factor kappa-beta.
abstract: Vascular endothelial cells respond to biomechanical forces, such as cyclic stretch and shear stress, by altering gene expression. Since endothelial-derived prostanoids, such as prostacyclin and thromboxane A(2), are key mediators of endothelial function, we investigated the effects of cyclic stretch on the expression of genes in human umbilical vein endothelial cells controlling prostanoid synthesis: cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), prostacyclin synthase (PGIS) and thromboxane A(2) synthase (TXAS). COX-2 and TXAS mRNAs were upregulated by cyclic stretch for 24h. In contrast, PGIS mRNA was decreased and stretch had no effect on COX-1 mRNA expression. We further show that stretch-induced upregulation of COX-2 is mediated by activation of the NF-kappabeta signaling pathway.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Haige
authors.initials: H
authors.lastname: Zhao
authors.forename: Toyoko
authors.initials: T
authors.lastname: Hiroi
authors.forename: Baranda S
authors.initials: BS
authors.lastname: Hansen
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Rade
mesh_terms: D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004730:Endothelium, Vascular / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D033081:Shear Strength; D013314:Stress, Mechanical
chemical_list: D016328:NF-kappa B; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human