title: p38 Mitogen-activated protein kinase activation in endothelial cell is implicated in cell alignment and elongation induced by fluid shear stress.
abstract: Fluid shear stress is thought to be important in maintaining the phenotype of endothelial cells (ECs) in vivo. The purpose of the study was to determine the effect of varying levels of laminar shear stress on EC elongation and alignment and the role of p38 mitogen-activated protein kinase (MAPK) on the morphologic change induced by shear stress. Cultured bovine aortic ECs were subjected to 1, 4, 7, 14, or 20 dyne/cm(2) laminar steady shear stress. On morphometric analysis of static ECs, the average orientation angle was 41 degrees , whereas after 24 h shear stress at 1, 4, 7, 14, and 20 dyne/cm(2) the angles were 34 degrees, 33 degrees, 16 degrees, 11 degrees, and 10 degrees, respectively. The shape index of static ECs was 0.76, whereas the indexes of ECs exposed to shear stress were 0.72, 0.72, 0.65, 0.50, and 0.47, respectively. The time and the magnitude of activation of p38 MAPK were dependent on the level of shear stress. The results indicate that a minimum shear stress of 7 to 14 dynes/cm(2) is necessary for cell alignment and elongation and this correlates with activity of p38 MAPK. ECs exposed to shear stress in the presence of the p38 MAPK inhibitor SB-203580 did not orient in any manner and the shape index was similar to the static cells.
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kadohama
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Akasaka
authors.forename: Kengo
authors.initials: K
authors.lastname: Nishimura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Sasajima
authors.forename: Bauer E
authors.initials: BE
authors.lastname: Sumpio
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D050197:Atherosclerosis / Q000201:enzymology / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D001808:Blood Vessels / Q000166:cytology / Q000201:enzymology*; D002417:Cattle; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D012039:Regional Blood Flow / Q000502:physiology; D013314:Stress, Mechanical; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000906:Antibodies; D004791:Enzyme Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases