Schematics of the principal effects of ATRA on the vascular endothelium. (1) ATRA induces the expression of endothelial cells (EC) TM, the membrane receptor that binds and inactivates thrombin; the TM/thrombin complex activates the protein C/protein S system, a potent anticoagulant mechanism; (2) ATRA prevents the expression of TF, the tissue procoagulant exposed by EC upon appropriate stimuli; (3) ATRA induces the EC production of t-PA and, to minor extent, of PAI-1, favoring the fibrinolytic response of the endothelium; (4) finally, ATRA counteracts the prothrombotic effects of cytokines, ie, IL-1β and TNF-α, on EC.