Thank you for the opportunity to respond to the letter by Drs. Witkowski and Rauch about our editorial. It is very challenging moving from in vitro studies with cultured cells to in vivo studies that analyze gene expression. In the tissue factor(TF) field it is well accepted that cultured endothelial cells(EC) do not express TF under basal conditions but can be induced to express TF after stimulation with a variety of agonists. Witkowski and Rauch state that the induction of TF in culture ECs “makes itlikelythatTFderivedfromECs contributes to coagulation under pathological conditions”. However, the models they present in support of arole for ECTF in coagulation are not selective for TF. For instance, over-expression of an NFκB inhibitor or EC-specific knock-out of miR-126 will affect many genes in the endothelium. Interestingly, miR-126 also regulates TF expression in monocytes. Furthermore,blood vessels are surrounded by pericytes, smooth muscle cells and adventitial fibroblasts, all of which express TF. Therefore, it is very difficult to distinguish the contribution of TF expression induced in the endothelium from that exposed on perivascular cells due to disruption of the endothelialbarrier
