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

  • Authors:
    • Xuefeng Shan
    • Zhiqiang Liu
    • Muhuyati Wulasihan
    • Songfeng Ma
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Surgery, The First Affiliated Hospital, Xinjiang Medical University, Urumchi, Xinjiang 830054, P.R. China, Comprehensive Heart Internal Medicine, Heart Center of The First Affiliated Hospital, Xinjiang Medical University, Urumchi, Xinjiang 830054, P.R. China
    Copyright: © Shan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3509-3517
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    Published online on: March 13, 2019
       https://doi.org/10.3892/etm.2019.7379
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Abstract

Thromboembolism is a commonly observed condition in geriatrics that is caused by vascular endothelial injury, platelet activation, physiological coagulation processes, reduction of anticoagulant activity, decreased fibrinolytic activity and abnormal flow in the heart chamber, artery or vein. The protein C anticoagulant system serves a crucial role in anticoagulant therapy for the treatment of thromboembolism. Previous findings have suggested that edoxaban is an efficient oral anticoagulant in the acute treatment of venous thromboembolism. In the present study, the efficacy of edoxaban on thromboembolism induced by atrial fibrillation was investigated in a mouse model. Inflammatory factors interleukin (IL)‑1, ‑4, ‑8 and tumor necrosis factor (TNF)‑α were analyzed in the sera of mice with fibrillation induced by thromboembolism. Expression and activity of thymic stromal lymphopoietin (TSLP) and activated protein C resistance were investigated in platelets and vascular endothelial cells (VECs). TSLP‑induced platelet viability, Wnt‑β phosphorylation and integrin expression were analyzed in platelets. Furthermore, Wnt‑β expression and the phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathway in VECs were analyzed. Results demonstrated that the expression levels of IL‑1, ‑4, ‑8 and TNF‑α were significantly downregulated in the sera of mice with fibrillation and thromboembolism following treatment with edoxaban (P<0.01). Furthermore, the expression levels of prostacyclin (PGI2), prostaglandin (PG)E2, PGD2 and PGF2α were significantly increased in the sera of experimental mice that received edoxaban therapy (P<0.01). Results also indicated that edoxaban significantly stimulated the protein expression of TSLP and activated Wnt‑β phosphorylation and integrin expression in platelets (P<0.01). In addition, edoxaban therapy significantly upregulated the expression levels of PI3K and AKT, and subsequently increased the activity of protein C and S in VECs (P<0.01). Notably, edoxaban treatment improved atrial fibrillation and thromboembolism, as determined by pathological analysis. In conclusion, these results suggested that edoxaban elicited beneficial effects for mice with atrial fibrillation induced by thromboembolism through the regulation of the Wnt‑β‑induced PI3K/ATK‑activated protein C system.
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Copy and paste a formatted citation
Spandidos Publications style
Shan X, Liu Z, Wulasihan M and Ma S: Edoxaban improves atrial fibrillation and thromboembolism through regulation of the Wnt‑β‑induced PI3K/ATK‑activated protein C system. Exp Ther Med 17: 3509-3517, 2019.
APA
Shan, X., Liu, Z., Wulasihan, M., & Ma, S. (2019). Edoxaban improves atrial fibrillation and thromboembolism through regulation of the Wnt‑β‑induced PI3K/ATK‑activated protein C system. Experimental and Therapeutic Medicine, 17, 3509-3517. https://doi.org/10.3892/etm.2019.7379
MLA
Shan, X., Liu, Z., Wulasihan, M., Ma, S."Edoxaban improves atrial fibrillation and thromboembolism through regulation of the Wnt‑β‑induced PI3K/ATK‑activated protein C system". Experimental and Therapeutic Medicine 17.5 (2019): 3509-3517.
Chicago
Shan, X., Liu, Z., Wulasihan, M., Ma, S."Edoxaban improves atrial fibrillation and thromboembolism through regulation of the Wnt‑β‑induced PI3K/ATK‑activated protein C system". Experimental and Therapeutic Medicine 17, no. 5 (2019): 3509-3517. https://doi.org/10.3892/etm.2019.7379
Copy and paste a formatted citation
x
Spandidos Publications style
Shan X, Liu Z, Wulasihan M and Ma S: Edoxaban improves atrial fibrillation and thromboembolism through regulation of the Wnt‑β‑induced PI3K/ATK‑activated protein C system. Exp Ther Med 17: 3509-3517, 2019.
APA
Shan, X., Liu, Z., Wulasihan, M., & Ma, S. (2019). Edoxaban improves atrial fibrillation and thromboembolism through regulation of the Wnt‑β‑induced PI3K/ATK‑activated protein C system. Experimental and Therapeutic Medicine, 17, 3509-3517. https://doi.org/10.3892/etm.2019.7379
MLA
Shan, X., Liu, Z., Wulasihan, M., Ma, S."Edoxaban improves atrial fibrillation and thromboembolism through regulation of the Wnt‑β‑induced PI3K/ATK‑activated protein C system". Experimental and Therapeutic Medicine 17.5 (2019): 3509-3517.
Chicago
Shan, X., Liu, Z., Wulasihan, M., Ma, S."Edoxaban improves atrial fibrillation and thromboembolism through regulation of the Wnt‑β‑induced PI3K/ATK‑activated protein C system". Experimental and Therapeutic Medicine 17, no. 5 (2019): 3509-3517. https://doi.org/10.3892/etm.2019.7379
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