Figure 4.

The prostacyclin axis-induced thrombosis protection. PK and B2R deficiency produces thrombosis protection through the prostacyclin axis. In the absence of PK or the B2R, there is increased prostacyclin production due to overexpression of the AT2R and/or Mas receptors to compensate for reduced or absent B2R. Prostacyclin induces a graded increase in thrombosis protection. First, at levels up to twofold increased, it effects the vessel wall reducing TF production. Second, at levels up to twofold to threefold increased, it downregulates vessel wall TF and induces a selective platelet function defect of reduced GPVI activation and spreading on collagen- and integrin-binding adhesive glycoproteins. Finally, at levels greater that threefold, prostacyclin produces the overall platelet anesthesia generally recognized with it.