Impact of Endothelial Microparticles on Coagulation, Inflammation, and Angiogenesis in Age-Related Vascular Diseases

Figure 2

Signaling pathways involved in thrombin induced EMP formation. EMPs carry TF, the main initiator of the extrinsic pathway of the coagulation cascade. Cofactor VIIIa known as a von Willebrand factor activates factor X to Xa in the presence of factor Va, calcium, and phospholipids (PL), which results in the generation of thrombin. Thrombin induces tumor necrosis factor alpha (TNFα) via p38 (mitogen activated protein kinase) and interleukins 1, 6, and 8 (Il-1, IL-6, and IL-8), which both lead to formation of EMPs. Thrombin, via proteolytically activated receptor-1 (PAR-1), induces nuclear factor kappa B (NF-κB), which directly induces EMP formation. PAR-1 also induces Rho kinase (ROCK- II) which activates caspase-2 leading to EMPs formation. Thrombin via (tumor necrosis factor related apoptosis inducing ligand) TRAIL activates sTRAIL, which is synthesized to TRAIL R2. This process requires the activation of NF-κB.