title: Laminar shear stress upregulates integrin expression: role in endothelial cell adhesion and apoptosis.
abstract: Laminar shear stress exerts important effects on endothelial cell (EC) function and inhibits apoptosis of ECs induced by various stimuli. The mechanism by which hemodynamic forces, such as shear stress, are transduced into cellular signaling is still not known. Located at the cell surface, integrins, which are required for cell adhesion and cell survival, are potential mechanotransducers. Therefore, we investigated the effect of shear stress on integrin expression in ECs. Shear stress time-dependently increased the mRNA expression of the fibronectin receptor subunits alpha(5) and beta(1) with a maximum at 6 hours (283+/-41% and 215+/-27% of control, respectively). In addition, the protein levels of the fibronectin receptor subunits alpha(5) and beta(1) were enhanced with a maximum at 12 hours of shear stress exposure (343+/-53% and 212+/-38% of control, respectively). The shear stress-induced upregulation of integrins is independent of nitric oxide. Furthermore, we confirmed the enhanced functional activity of alpha(5)beta(1) integrin expression by FACS analysis. As a functional consequence, human umbilical vein ECs, which were preexposed to shear stress, revealed a significantly increased attachment (178+/-10% of static controls) and a more pronounced extracellular signal-regulated kinase 1 and 2 activation in response to cell attachment. Finally, we demonstrated that shear stress requires RGD-sensitive integrins to mediate its antiapoptotic effect. Taken together, these results define a novel mechanism by which shear stress may exert its atheroprotective effects via upregulation of integrins to support EC adhesion and survival.
authors.affiliation: Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Urbich
authors.forename: D H
authors.initials: DH
authors.lastname: Walter
authors.forename: A M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: S
authors.initials: S
authors.lastname: Dimmeler
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D020411:Oligonucleotide Array Sequence Analysis; D009842:Oligopeptides / Q000494:pharmacology; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000096:biosynthesis; D017469:Receptors, Fibronectin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D015854:Up-Regulation
chemical_list: D009842:Oligopeptides; D012333:RNA, Messenger; D017469:Receptors, Fibronectin; D009569:Nitric Oxide; C047981:arginyl-glycyl-aspartic acid; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases