title: Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells.
abstract: Hemodynamic forces induce various functional changes in vascular endothelium, many of which reflect alterations in gene expression. We have recently identified a cis-acting transcriptional regulatory element, the shear stress response element (SSRE), present in the promoters of several genes, that may represent a common pathway by which biomechanical forces influence gene expression. In this study, we have examined the effect of shear stress on endothelial expression of three adhesion molecules: intercellular adhesion molecule-1 (ICAM-1), which contains the SSRE in its promoter, and E-selectin (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1), both of which lack the SSRE. Cultured human umbilical vein endothelial cells, subjected to a physiologically relevant range of laminar shear stresses (2.5-46 dyn/cm2) in a cone and plate apparatus for up to 48 h, showed time-dependent but force-independent increases in surface immunoreactive ICAM-1. Upregulated ICAM-1 expression was correlated with increased adhesion of the JY lymphocytic cell line. Northern blot analysis revealed increased ICAM-1 transcript as early as 2 h after the onset of shear stress. In contrast, E-selectin and vascular cell adhesion molecule-1 transcript and cell-surface protein were not upregulated at any time point examined. This selective regulation of adhesion molecule expression in vascular endothelium suggests that biomechanical forces, in addition to humoral stimuli, may contribute to differential endothelial gene expression and thus represent pathophysiologically relevant stimuli in inflammation and atherosclerosis.
authors.affiliation: Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge, Massachusetts 02139.
authors.forename: T
authors.initials: T
authors.lastname: Nagel
authors.forename: N
authors.initials: N
authors.lastname: Resnick
authors.forename: W J
authors.initials: WJ
authors.lastname: Atkinson
authors.forename: C F
authors.initials: CF
authors.lastname: Dewey
authors.forename: M A
authors.initials: MA
authors.lastname: Gimbrone
mesh_terms: D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D012333:RNA, Messenger / Q000032:analysis; D013314:Stress, Mechanical; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1