title: Endothelial cell response to biomechanical forces under simulated vascular loading conditions.
abstract: In vivo, endothelial cells (EC) are constantly exposed to the haemodynamic forces (HF) of pressure, wall shear stress and hoop stress. The main aim of this study was to design, create and validate a novel perfusion bioreactor capable of delivering shear stress and intravascular pressure to EC in vitro and to characterise their morphology, orientation and gene expression. Here we report the creation and validation of such a simulator and the dual application of pressure (120/60 mmHg) and low shear stress (5 dyn/cm(2)) to a monolayer of EC established on a non-compliant silicone tube. Under these conditions, EC elongated and realigned obliquely to the direction of applied shear stress in a time-dependent manner. Furthermore, randomly distributed F-actin microfilaments reorganised into long, dense stress fibres crossing the cells in a direction perpendicular to that of flow. Finally, combinatorial biomechanical conditioning of EC induced the expression of the inflammatory-associated E-selectin gene.
authors.affiliation: National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
authors.forename: M A
authors.initials: MA
authors.lastname: Punchard
authors.forename: C
authors.initials: C
authors.lastname: Stenson-Cox
authors.forename: E D
authors.initials: ED
authors.lastname: O'cearbhaill
authors.forename: E
authors.initials: E
authors.lastname: Lyons
authors.forename: S
authors.initials: S
authors.lastname: Gundy
authors.forename: L
authors.initials: L
authors.lastname: Murphy
authors.forename: A
authors.initials: A
authors.lastname: Pandit
authors.forename: P E
authors.initials: PE
authors.lastname: McHugh
authors.forename: V
authors.initials: V
authors.lastname: Barron
mesh_terms: D000199:Actins / Q000378:metabolism; D019149:Bioreactors; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003198:Computer Simulation; D019040:E-Selectin / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D011312:Pressure; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: D000199:Actins; D019040:E-Selectin; D018799:Intercellular Adhesion Molecule-1