Figure 1.

Pathophysiology for thrombosis protection in prekallikrein (PK)-deleted mice. In the absence of PK, there is a decrease in plasma bradykinin (BK) and the BK B2 receptor (B2R). Lower BK and B2R are associated with a reduction in the expression of the renin-angiotensin receptor angiotensin receptor 2 (AT2R). Surprisingly, the Mas receptor becomes overexpressed leading to a 1.5- to 2.0-fold increase in prostacyclin. This elevation of PGI₂ is not enough to inhibit platelets, but is sufficient to elevate vessel wall Sirt1 and KLF4 that together reduce tissue factor (TF) expression. In this mouse model, reduction of TF appears to be sufficient to reduce thrombosis risk in klkb1^−/− mice.