Figure 3.

Mechanisms for thrombosis delay in the bradykinin B2 receptor-deleted mice. In the absence of the bradykinin B2 receptor (B2R), there is increased plasma bradykinin (BK), its ACE breakdown product, BK-(1–5) (RPPGF). There is also increased ACE, angiotensin II (AngII), and angiotensin-(1–7) [Ang-(1–7)]. Elevated AngII and Ang-(1–7) bind to increased angiotensin receptor 2 (AT2R) and Mas to increase prostacyclin (PGI₂) levels twofold to threefold above normal. This elevation in plasma PGI₂ results in increased vessel wall Sirt1 and KLF4 with reduced TF and a selective platelet function defect. The selective platelet function defect is reduced GPVI activation with normal thrombin- and ADP-induced platelet activation and reduced spreading on collagen and adhesive glycoproteins through β1 integrin binding. The delayed thrombosis in B2R-deficient mice is reduced vessel wall tissue factor a selective platelet function defect of GPVI activation and spreading.