Edoxaban improves atrial fibrillation and thromboembolism through regulation of the Wnt‑β‑induced PI3K/ATK‑activated protein C system

Figures

• 

  Figure 1.. Effects of edoxaban on inflammatory factors and chemokines in the sera of mice with atrial fibrillation and vein thrombus. Plasma levels of (A) IL-1, (B) IL-4, (C) IL-8 and (D) TNF-α, (E) PGI2, (F) PGE2, (G) PGD2 and (H) PGF2α in mice with fibrillation and vein thrombus treated with edoxaban or phosphate-buffered saline. Data are presented as the mean ± standard deviation of the mean. **P<0.01 as indicated. IL, interleukin; TNF, tumor necrosis factor; PG, prostaglandin.

• 

  Figure 2.. Analysis of TSLP expression and protein C system activity in mice with atrial fibrillation and vein thrombus. (A-D) Protein expression levels of TSLP, PC, PS, TM, APCI, P-selectin and integrin αIIbβ3 in experimental mice treated with edoxaban or phosphate-buffered saline. Data are presented as mean ± standard deviation of the mean. **P<0.01 as indicated. TSLP, thymic stromal lymphopoietin; PC, protein C; PS, protein S; TM, thrombomodulin; APCI, activated protein C inhibitor.

• 

  Figure 3.. Effects of edoxaban on Wnt-β phosphorylation, and platelet aggregation and secretion in mice with atrial fibrillation and vein thrombus. (A) Wnt-β phosphorylation in platelets in edoxaban-treated mice with atrial fibrillation and vein thrombus. (B) Aggregation of platelet cells in experimental mice. (C) Protein expression levels of thrombin and (D) platelet serotonin release in mice with atrial fibrillation and vein thrombus. All data are presented as the mean ± standard deviation of the mean. **P<0.01 as indicated.

• 

  Figure 4.. Edoxaban regulates the protein C system through the Wnt-β-mediated PI3K/AKT signal pathway in VECs. (A) Expression levels of PI3K and AKT in VEC in experimental mice. (B) Wnt-β expression levels in VEC in Edoxaban-treated mice with atrial fibrillation and vein thrombus. (C) Effects of Si-Wnt-β on Expression levels of PI3K and AKT in VEC in Edoxaban-treated mice with atrial fibrillation and vein thrombus. (D) Effects of Si-Wnt-β on Expression levels of PC and PS in VEC in Edoxaban-treated mice with atrial fibrillation and vein thrombus. (E) Expression levels of TM and APCI were downregulated by Si-Wnt-β. (F) Effects of Si-Wnt-β on Expression levels of TSLP and integrin in VEC in Edoxaban-treated mice with atrial fibrillation and vein thrombus. All data are presented as the mean ± standard deviation of the mean. **P<0.01 as indicated. VEC, vascular endothelial cells; PI3K, phosphoinositide 3-kinase; AKT, protein kinase B; TM, thrombomodulin; APCI, activated protein C inhibitor; TSLP, thymic stromal lymphopoietin; PS, protein S; PC, protein C.

• 

  Figure 5.. Effects of edoxaban on stroke, atrial fibrillation and vein thrombus in mice with atrial fibrillation and vein thrombus. (A) Apoptosis of vascular endothelial cells in mice treated with edoxaban or phosphate-buffered saline (magnification, ×200). (B) Effects of edoxaban on thrombus formation in the mice model of atrial fibrillation and vein thrombus. Efficacy of edoxaban was analyzed on (C) stroke and (D) blood velocity in experimental mice treated with edoxaban or phosphate-buffered saline. Effects of (E) atrial fibrillation and (F) area of vein thrombus in mice with atrial fibrillation and vein thrombus treated with edoxaban or phosphate-buffered saline (magnification, ×200). The black box indicates vein thrombus. All data are presented as the mean ± standard deviation of the mean. **P<0.01 as indicated.