Sphingosine-1-Phosphate and Its Receptors: A Mutual Link between Blood Coagulation and Inflammation

Figure 3

The coagulation proteases thrombin and activated factor X (FXa) enhance S1P synthesis and release from vascular smooth muscle cells (VSCMs). During vascular injury, local generation of thrombin and FXa enhances the synthesis and the release of S1P via activation of PAR-1 and PAR-2, respectively. This signaling pathway involves activation of the small GTPase Rho and PKC signaling leading to transcriptional upregulation of SphK-1. The resulting S1P activities regulate proliferation and migration of VSMCs.