title: Impact of Bi-Axial Shear on Atherogenic Gene Expression by Endothelial Cells.
abstract: This study demonstrated the effects of the directionality of oscillatory wall shear stress (WSS) on proliferation and proatherogenic gene expression (I-CAM, E-Selectin, and IL-6) in the presence of inflammatory mediators leukotriene B4 (LTB4) and bacterial lipopolysaccharide (LPS) from endothelial cells grown in an orbiting culture dish. Computational fluid dynamics (CFD) was applied to quantify the flow in the dish, while an analytical solution representing an extension of Stokes second problem was used for validation. Results indicated that WSS magnitude was relatively constant near the center of the dish and oscillated significantly (0-0.9 Pa) near the side walls. Experiments showed that LTB4 dominated the shear effects on cell proliferation and area. Addition of LPS didn't change proliferation, but significantly affected cell area. The expression of I-CAM1, E-Selectin and IL-6 were altered by directional oscillatory shear index (DOSI, a measure of the biaxiality of oscillatory shear), but not shear magnitude. The significance of DOSI was further reinforced by the strength of its interactions with other atherogenic factors. Hence, directionality of shear appears to be an important factor in regulating gene expression and provides a potential explanation of the propensity for increased vascular lesions in regions in the arteries with oscillating biaxial flow.
authors.affiliation: Department of Chemical Engineering, University of Louisville, Ernst Hall 106, Louisville, KY, 40292, USA.
authors.forename: Amlan
authors.initials: A
authors.lastname: Chakraborty
authors.affiliation: Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, USA.
authors.forename: Sutirtha
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: James Graham Brown Cancer Center and Department of Microbiology & Immunology, University of Louisville, CTRB, Room #324, Louisville, KY, 40202, USA.
authors.forename: Venkatakrishna R
authors.initials: VR
authors.lastname: Jala
authors.affiliation: Department of Chemical Engineering, University of Louisville, Ernst Hall 106, Louisville, KY, 40292, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Thomas
authors.affiliation: Department of Mechanical Engineering, University of Louisville, Louisville, KY, USA.
authors.forename: M Keith
authors.initials: MK
authors.lastname: Sharp
authors.affiliation: Department of Chemical Engineering, University of Louisville, Ernst Hall 106, Louisville, KY, 40292, USA. eric.berson@louisville.edu.
authors.forename: R Eric
authors.initials: RE
authors.lastname: Berson
authors.affiliation: James Graham Brown Cancer Center and Department of Microbiology & Immunology, University of Louisville, CTRB, Room #324, Louisville, KY, 40202, USA. h0bodd01@louisville.edu.
authors.forename: Bodduluri
authors.initials: B
authors.lastname: Haribabu
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D019040:E-Selectin / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008955:Models, Cardiovascular; D033081:Shear Strength
chemical_list: D019040:E-Selectin; C573420:ICAM1 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; D007975:Leukotriene B4
keywords: Atherogenic gene expression; Computational fluid dynamics; Directionality of shear; Endothelial cellular responses; Oscillatory shear stress; Statistical significance