EXPRESSION OF TISSUE FACTOR IN THE RABBIT AORTA AFTER BALLOON INJURY

Tissue factor (TF) is a primary initiator of the extrinsic pathway of blood coagulation. Recently TF has been shown to be overexpressed in a therosclerotic lesions and it is thought to contribute to the thrombog enicity of the plaques. We studied TF expression in the media and the neointima of rabbit aortas at various intervals after balloon injury. TF protein was immunohistochemically detected in smooth muscle cells ( SMCs) of the inner layer of the media at 2 h after injury and was subs equently detected in SMCs in the neointima, whereas no TF expression w as detected in the uninjured aortas except for the adventitia. Immunoh istochemical and immunoelectron microscopic studies revealed that TF-p ositive SMCs were of an immature or synthetic phenotype and TF protein was detected in the rough endoplasmic reticulum in SMCs. TF mRNA in t he intima and media increased at 2 h after injury and returned to near baseline levels at 12-24 h, whereas TF activity also increased at 2 h and continued at similar levels over the next 72 h. TF mRNA and activ ity increased markedly at 2-8 weeks after injury. These data suggest t hat TF is rapidly induced in the medial SMCs and hereafter is constitu tively expressed in the neointima. TF expressed in the neointima may c ontribute to hypercoagulable properties of injured arteries. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.