Expression of Tissue Factor in Experimental Anastomotic Pseudoaneurysm

Abstract

Tissue factor (TF) is a potent initiator of the coagulation cascade and plays a critical role in arterial thrombosis. It is expressed in the adventitia of normal arteries and is induced in medial smooth muscle cells (SMC) by arterial injury. TF is also likely to be expressed in pseudoaneurysms, which are essentially contained disruptions of the arterial wall. The components of the pseudoaneurysm wall and the distribution of TF in particular have not been reported. To examine this we employed an experimental model of pseudoaneurysm in the rat carotid artery. Eight pseudoaneurysms were generated by microsurgical anastomosis and analyzed by histology and immunohistochemistry. Balloon injured carotids and normal carotids were used for comparison. The pseudoaneurysm wall was formed by SMC and extracellular matrix, similar to the neointima of injured arteries. However, TF was found predominantly in the adventitial aspect of the pseudoaneurysm wall, as opposed to a diffuse distribution throughout the neointima of balloon injured arteries. TF antigen was not seen on or near the luminal border of the pseudoaneurysm wall. Microscopic examination and staining for von Willebrand factor antigen showed no evidence of endothelium in the pseudoaneurysm. The authors hypothesize that spontaneous thrombotic occlusion may not occur because TF is not present at the luminal surface. The efficacy of compression therapy for pseudoaneurysm may be dependent on the ability to cause sufficient disruption of the wall to expose TF found in the deeper layers of the arterial wall to circulating blood. The present model may be useful to further define the determinants regulating pseudoaneurysm closure.