Identification of active tissue factor in human coronary atheroma.
BACKGROUND
Recent observations suggest that thrombosis in vivo is initiated via the tissue factor (TF) pathway. The TF activity of human coronary atheroma has not been reported.


RESULTS
Directional coronary atherectomy (DCA) specimens from 63 lesions were analyzed with the use of a quantitative TF-specific activity assay. The median content of TF was 10 ng/g plaque (95% CI, 6 to 13 ng/g; range, 0 to 47 ng/g). After homogenization of the specimens, TF activity was detected in 28 of 31 lesions (90%). With a polyclonal anti-human TF antibody, the use of immunohistochemistry detected TF antigen in 43 of 50 lesions (86%); TF antigen was expressed in cellular and acellular areas of the plaque. Histologically defined thrombus was present in 19 of the 43 lesions with detectable TF antigen and in none of the 7 lesions without detectable TF antigen (19 of 43 versus 0 of 7; P < .02). TF antigen was undetectable with immunohistochemistry in 4 of 13 restenotic lesions (31%) and in 3 of 37 de novo lesions (8%) (P < .05).


CONCLUSIONS
TF contributes to the procoagulant activity of most atherosclerotic lesions treated with DCA. The association of immunohistochemically detectable TF with plaque thrombus suggests that TF plays a role in coronary thrombosis. Diminished TF expression in restenotic lesions may in part account for the lower complication rate that has been associated with DCA of restenotic versus de novo lesions. Inhibition of TF may represent a therapeutic goal for the prevention of thrombotic complications associated with percutaneous coronary interventions.
Marmur
J D
JD
Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029-6574, USA. jmarmur@smtplink.mssm.edu
Thiruvikraman
S V
SV
Fyfe
B S
BS
Guha
A
A
Sharma
S K
SK
Ambrose
J A
JA
Fallon
J T
JT
Nemerson
Y
Y
Taubman
M B
MB
D000941:Antigens / Q000032:analysis; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001682:Biological Availability; D003324:Coronary Artery Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015951:Factor Xa / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D013194:Staining and Labeling; D013925:Thromboplastin / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
D000941:Antigens; D013925:Thromboplastin; D015951:Factor Xa