TISSUE FACTOR IS RAPIDLY INDUCED IN ARTERIAL SMOOTH-MUSCLE AFTER BALLOON INJURY

Tissue factor (TF) is a major activator of the coagulation cascade and may play a role in initiating thrombosis after intravascular injury. To investigate whether medial vascular smooth muscle provides a source of TF following arterial injury, the induction of TF mRNA and protein was studied in balloon-injured rat aorta. After full length aortic in jury, aortas were harvested at various times and the media and adventi tia separated using collagenase digestion and microscopic dissection. In uninjured aortic media, TF mRNA was undetectable by RNA blot hybrid ization. 2 h after balloon injury TF mRNA levels increased markedly. R eturn to near baseline levels occurred at 24 h. In situ hybridization with a S-35-labeled antisense rat TF cRNA probe detected TF mRNA in th e adventitia but not in the media or endothelium of uninjured aorta. 2 h after balloon dilatation, a marked induction of TF mRNA was observe d in the adventitia and media. Using a functional clotting assay, TF p rocoagulant activity was detected at low levels in uninjured rat aorti c media and rose by almost-equal-to 10-fold 2 h after balloon dilatati on. Return to baseline occurred within 4 d. These data demonstrate tha t vascular injury rapidly induces active TF in arterial smooth muscle, providing a procoagulant that may result in thrombus initiation or pr opagation.