title: Tissue factor expression in atrial endothelia associated with nonvalvular atrial fibrillation: possible involvement in intracardiac thrombogenesis.
abstract: BACKGROUND
  Tissue factor plays a key role in the extrinsic coagulation pathway and is induced by inflammatory cytokines. Atrial myocarditis has been detected recently in some patients with lone atrial fibrillation. Virchow's triad of low blood flow, hypercoagulability, and endothelial dysfunction, enhances thrombus formation. The present study was designed to elucidate the role of endothelial dysfunction in thrombogenesis associated with nonvalvular atrial fibrillation.
  
  
  METHODS
  We investigated tissue factor expression in the endothelia of left atrial appendages obtained from seven patients with nonvalvular atrial fibrillation and cardiogenic thromboembolism. Tissues were divided into 7-13 sections and compared with control specimens from four patients who died of noncardiac events. Expression of tissue factor, von Willebrand factor and tissue factor pathway inhibitor was evaluated by immunohistochemistry.
  
  
  RESULTS
  Histopathologically, inflammatory cells infiltrated the endocardium and all seven patients showed features of persistent myocarditis. Activated T cells [15.3+/-9.4 cells/high power field (HPF, mean+/-S.D.) vs. control 2.2+/-4.4/HPF (P=0.0294)] and a few macrophages [5.1+/-8.4 cells/HPF vs. control 2.4+/-3.5 cells/HPF (P=NS)] infiltrated the endocardium. Tissue factor was overexpressed in the endothelia particularly in tissues containing inflammatory cells and denuded matrix of the endocardium, compared with the control group. Von Willebrand factor, but not tissue factor pathway inhibitor, was also overexpressed in these tissues.
  
  
  CONCLUSIONS
  Tissue factor expression induced by local inflammation is involved in the pathogenesis of thrombosis in patients with nonvalvular atrial fibrillation.
authors.affiliation: Department of Cardiovascular Medicine, Matsuyama Shimin Hospital, 2-6-5, Ohte-machi, Ehime, 790-0067, Matsuyama, Japan. ynakamur@mti.biglobe.ne.jp
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kengo
authors.initials: K
authors.lastname: Fukushima-Kusano
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohta
authors.forename: Hiromi
authors.initials: H
authors.lastname: Matsubara
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hamuro
authors.forename: Chikao
authors.initials: C
authors.lastname: Yutani
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohe
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000473:pathology*; D004699:Endocardium / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006325:Heart Atria / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000378:metabolism / Q000473:pathology; D013925:Thromboplastin / Q000096:biosynthesis*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor; D013925:Thromboplastin