FURTHER-STUDIES ON THE PRESENCE OF FUNCTIONAL TISSUE FACTOR ACTIVITY ON THE SUBENDOTHELIUM OF NORMAL HUMAN AND RABBIT ARTERIES

Although tissue factor (TF) activity has been observed on the subendot helial surface of rabbit aorta and human umbilical cord, immunofluores cent and in situ hybridization methods have failed repeatedly to demon strate TF in the intima of human blood vessels. In the present study, TF activity on everted, de-endothelialized arteries was studied by two methods. One utilized a flow system and measured fibrin deposition an d fibrinopeptide A formation. The other utilized a newly developed rot ating probe system and measured the conversion of factor X to factor X a in the presence of factor VIIa and Ca+2 The study attempted to contr ol, or assess, the possibility that functional TF could have been expo sed on the vessel surface by the procedures used to prepare the arteri al segments. By both methods, TF activity was detected on the subendot helium of rabbit aortae and human umbilical arteries, and was unaffect ed by the length of storage or by inclusion of actinomycin D in the st orage buffer. TF activity was also observed in the subendothelium of a dult human ileo-colic, internal mammary, and renal arteries, studied b y the rotating probe method. The latter may underestimate TF activity, as some of the factor Xa formed appears to bind to the subendothelial surface. TF activity (Xa formation) was detected on the luminal surfa ce (subendothelium) of non-everted arteries, but increased activity wa s observed after eversion of the vessel. The source of the subendothel ial TF, and its presence in normal subendothelium in vivo, requires fu rther study. In addition, if any of the TF activity observed in this s tudy was derived from injured endothelial or myointimal cells during p reparation of the everted vessel segments, the techniques described co uld serve as a useful model for studying TF-induced thrombosis and fac tor Xa formation on injured blood vessels, and for evaluating the anti -thrombotic properties of TF-inhibitors.