Tissue factor expression in atrial endothelia associated with nonvalvular atrial fibrillation: possible involvement in intracardiac thrombogenesis.
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.
Nakamura
Yoichi
Y
Department of Cardiovascular Medicine, Matsuyama Shimin Hospital, 2-6-5, Ohte-machi, Ehime, 790-0067, Matsuyama, Japan. ynakamur@mti.biglobe.ne.jp
Nakamura
Kazufumi
K
Fukushima-Kusano
Kengo
K
Ohta
Keiko
K
Matsubara
Hiromi
H
Hamuro
Tsutomu
T
Yutani
Chikao
C
Ohe
Tohru
T
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
D014841:von Willebrand Factor; D013925:Thromboplastin