title: Platelets modulate endothelial cell response to dynamic shear stress through PECAM-1.
abstract: BACKGROUND
  Both vascular endothelial cells and platelets are sensitive to blood flow induced shear stress. We have recently reported that platelet-endothelial cell interaction could greatly affect platelet activation under flow. In the present study, we aimed to investigate how platelet-endothelial cell interaction affected endothelial cell inflammatory responses under flow.
  
  
  METHODS
  Human coronary artery endothelial cells were exposed to normal or low pulsatile shear stress with or without the presence of platelets. Following shear exposure, endothelial cell ICAM-1 expression was measured using ELISA, Western blot and PCR; cell surface PECAM-1 expression/phosphorylation was measured using ELISA. Platelet adhesion to endothelial cells was quantified using immunofluorescence microscopy. To determine the role of PECAM-1 in platelet-endothelial cell interaction, endothelial cell PECAM-1 expression was suppressed using siRNA.
  
  
  RESULTS
  Pathological low shear stress induced a significant increase in endothelial cell ICAM-1 expression, at both protein and mRNA levels. Platelet adhesion to endothelial cells increased significantly under low shear stress, co-localizing with PECAM-1 at endothelial cell junctions. The presence of platelets inhibited low shear stress-induced ICAM-1 upregulation. When endothelial cell PECAM-1 expression was suppressed, platelet adhesion to endothelial cells under low shear stress decreased significantly; endothelial cell ICAM-1 expression was not affected by shear stress, with or without platelets.
  
  
  CONCLUSIONS
  These results suggested that PECAM-1 could mediate platelet adhesion to endothelial cells under shear stress. Platelets binding to endothelial cells interfered with endothelial cell mechanotransduction through PECAM-1, affecting endothelial cell inflammatory responses towards pathological shear flow.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, United States.
authors.forename: Daphne
authors.initials: D
authors.lastname: Meza
authors.affiliation: School of Mechanical and Aerospace Engineering, Oklahoma State University, Stillwater, OK 74074, United States.
authors.forename: Saravan K
authors.initials: SK
authors.lastname: Shanmugavelayudam
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, United States.
authors.forename: Arielys
authors.initials: A
authors.lastname: Mendoza
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, United States.
authors.forename: Coralys
authors.initials: C
authors.lastname: Sanchez
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Rubenstein
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, United States; School of Mechanical and Aerospace Engineering, Oklahoma State University, Stillwater, OK 74074, United States. Electronic address: wei.yin@stonybrook.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Yin
mesh_terms: D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D010973:Platelet Adhesiveness; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D009569:Nitric Oxide
keywords: Endothelial cells; ICAM-1; PECAM-1; Platelets; Shear stress