title: Endogenous NO blockade enhances tissue factor expression via increased Ca2+ influx through MCP-1 in endothelial cells by monocyte adhesion.
abstract: OBJECTIVE
  Ca2+ plays an important role in tissue factor (TF) gene expression. We investigated the role of endogenous nitric oxide (NO) in the induction of TF expression in endothelial cells (ECs) by monocyte adhesion and the mechanisms of NO action.
  
  
  RESULTS
  Inhibition of endogenous NO by Nomega-nitro-L-arginine methyl ester (L-NAME) enhanced TF promoter activity and protein expression induced in human coronary ECs by monocyte adhesion, as well as EC surface TF activity. L-NAME also induced monocyte chemoattractant protein-1 (MCP-1) expression, which was blocked by an NO donor, NOC18. Exogenous MCP-1 enhanced TF expression induced by monocyte adhesion, whereas adenovirus-mediated expression of the mutant MCP-1, 7ND, abolished the L-NAME enhancement of TF expression induced by monocyte adhesion. Monocyte attachment to L-NAME-treated ECs increased Ca2+ influx, which was prevented by NOC18, anti-MCP-1 antibody or 7ND. These results indicate that the binding of increased MCP-1 induced by endogenous NO blockade to CCR2 mediated the enhancement of Ca2+ influx only when monocytes adhered to ECs, which upregulated TF expression in ECs triggered by monocyte adhesion.
  
  
  CONCLUSIONS
  MCP-1/CCR2 may play a role in Ca2+ influx-dependent TF regulation in the monocyte-EC interaction in the impairment of NO synthesis.
authors: First Department of Internal Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
authors: Takayuki
authors: T
authors: Sakamoto
authors: Toshiyuki
authors: T
authors: Ishibashi
authors: Nobuo
authors: N
authors: Sakamoto
authors: Koichi
authors: K
authors: Sugimoto
authors: Kensuke
authors: K
authors: Egashira
authors: Hiroshi
authors: H
authors: Ohkawara
authors: Kenji
authors: K
authors: Nagata
authors: Keiko
authors: K
authors: Yokoyama
authors: Masashi
authors: M
authors: Kamioka
authors: Toshihiro
authors: T
authors: Ichiki
authors: Naotoshi
authors: N
authors: Sugimoto
authors: Masahiko
authors: M
authors: Kurabayashi
authors: Koji
authors: K
authors: Suzuki
authors: Yoh
authors: Y
authors: Takuwa
authors: Yukio
authors: Y
authors: Maruyama
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003331:Coronary Vessels / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D013925:Thromboplastin; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester