title: Integral role of RhoA activation in monocyte adhesion-triggered tissue factor expression in endothelial cells.
abstract: OBJECTIVE
  The role of Rho activation in the regulation of tissue factor (TF) is not clear. This study was undertaken to investigate this in endothelial cells induced by monocyte adhesion.
  
  
  RESULTS
  Isolated human peripheral blood monocytes were added to cultured human coronary endothelial cells. Monocyte adhesion to endothelial cells increased the levels of TF antigen in the endothelial cells. The results of transient transfection of the human TF promoter/luciferase gene into endothelial cells indicated that the increase in endothelial expression of the TF gene caused by monocyte adhesion occurred at the transcriptional level. The upregulation of TF was inhibited by statins, and the suppressive effect of statins was reversed by geranylgeranylpyrophosphate. Monocyte adhesion rapidly upregulated the membrane translocation and GTP/GDP exchange of RhoA, but not of Cdc42 or Rac, in endothelial cells. Rho inhibition by C3 exoenzyme or adenovirus-mediated expression of N19RhoA prevented the endothelial upregulation of TF caused by monocyte adhesion, and this was mimicked by Rho-kinase inhibitors. Moreover, monocyte adhesion increased the phosphorylation of nuclear factor-kappaB p65 in endothelial cells, and this was prevented by statins and Rho inhibition.
  
  
  CONCLUSIONS
  Our study shows that RhoA activation plays an integral role in TF expression in endothelial cells.
authors.affiliation: First Department of Internal Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohkawara
authors.forename: Kenji
authors.initials: K
authors.lastname: Nagata
authors.forename: Koichi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Sotaro
authors.initials: S
authors.lastname: Sakurada
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Sugimoto
authors.forename: Atai
authors.initials: A
authors.lastname: Watanabe
authors.forename: Keiko
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurabayashi
authors.forename: Yoh
authors.initials: Y
authors.lastname: Takuwa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D018920:Coculture Techniques; D003331:Coronary Vessels / Q000166:cytology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017368:Protein Prenylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1; D006160:Guanosine Triphosphate; D013925:Thromboplastin; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein