Intimal Tissue Factor Activity Is Released from the Arterial Wall after Injury
Peter L. A. Giesen (1), (3), * , Billie S. Fyfe (4), * * , John T. Fallon (2), (3), (4) , Merce Roque (2), (3) , Milton Mendlowitz (3) , Maria Rossikhina (2), (3) , Arabinda Guha (1), (3) , Juan J. Badimon (2), (3) , Yale Nemerson (1), (3) , Mark B. Tau
From the (1) Division of Thrombosis Research and (2) The Zena and Michael A. Wiener Cardiovascular Institute, (3) Department of Medicine, and (4) Department of Pathology, The Mount Sinai School of Medicine, New York, NY, USA
Tissue factor (TF), the initiator of coagulation, has been implicated
as a critical mediator of arterial thrombosis. Previous studies have
demonstrated that TF is rapidly induced in the normal rodent arterial
wall by balloon injury, but is not associated with fibrin deposition.
A second injury, however, performed 10-14 days after the first, is
followed by small platelet-fibrin microthrombi. This study was undertaken
to better localize active TF in balloon-injured rat arteries and
to explore possible mechanisms underlying the apparent discrepancy
between injury-induced TF expression and the lack of large plateletfibrin
thrombi. By immunohistochemistry, TF antigen was first detected
in the media 24 h after injury to rat aortas, and subsequently accumulated
in the neointima. Using an ex vivo flow chamber, no TF
activity (Factor Xa generation) was found on the luminal surface of
normal or injured aortas. Wiping the luminal surface with a cotton swab
exposed TF activity in all vessels; levels were increased ≈3-fold in
arteries containing a neointima. The exposed TF activity was rapidly
washed into the perfusate, rendering the luminal surface inactive.
The loss of luminal TF into the circulation may attenuate thrombosis
at sites of arterial injury.