FXII regulates the formation of deep vein thrombosis via the PI3K/AKT signaling pathway in mice

Meng,Yan; Yin,Qian; Ma,Qiang; Qin,Hao; Zhang,Junbo; Zhang,Bo; Pang,Honggang; Tian,Hongyan

doi:10.3892/ijmm.2021.4920

FXII regulates the formation of deep vein thrombosis via the PI3K/AKT signaling pathway in mice

Authors:
- Yan Meng
- Qian Yin
- Qiang Ma
- Hao Qin
- Junbo Zhang
- Bo Zhang
- Honggang Pang
- Hongyan Tian
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Affiliations: Department of Peripheral Vascular Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: March 23, 2021 https://doi.org/10.3892/ijmm.2021.4920
Article Number: 87
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Deep vein thrombosis (DVT) is a common peripheral vascular disease, which may result in pulmonary embolism and is accompanied by endothelial injury. However, the pathogenesis of DVT remains unclear. Coagulation factor XII (FXII), as an important coagulation factor, has been reported to be closely associated with thrombosis. However, the association between FXII protein and DVT formation is not yet fully understood. The present study examined the effects of FXII protein on DVT formation and aimed to reveal the underlying mechanism. In the present study, histological characterization of the femoral vein tissue was examined by hematoxylin and eosin staining. The damage to the femoral vein tissue was examined by TUNEL assay. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were examined using ELISA. Tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑8 and phosphoinositide 3‑kinase (PI3K)/AKT signaling were determined by ELISA, immunohistochemical staining and western blot analysis. The results demonstrated that thrombosis, FXII protein, cell apoptosis and the SOD concentrations were decreased, while the MDA concentrations were increased in mice with DVT compared with the control or sham groups. TNF‑α, IL‑6, IL‑8 and PI3K/AKT signaling was also upregulated in the mice with DVT. Furthermore, the knockdown of FXII significantly upregulated the SOD concentrations and downregulated thrombosis and cell apoptosis, as well as the MDA concentrations in mice with DVT. The knockdown of FXII also significantly downregulated the protein expression of TNF‑α, IL‑6 and IL‑8, and the activation of PI3K/AKT signaling. Additionally, LY294002 pre‑treatment markedly downregulated thrombosis and cell apoptosis and the MDA content, whereas it upregulated the SOD concentrations in mice with DVT. LY294002 pre‑treatment also significantly downregulated the TNF‑α, IL‑6 and IL‑8 protein levels. Taken together, the present study demonstrates that FXII protein promotes DVT via the activation of PI3K/AKT signaling by inducing an inflammatory response. Targeting FXII protein may thus prove to be a potential approach for the treatment of DVT.

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