Department of Peripheral Vascular Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Int J Mol Med. 2021 May;47(5). doi: 10.3892/ijmm.2021.4920. Epub 2021 Mar 24.
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.
深静脉血栓形成（DVT）是一种常见的周围血管疾病，可能导致肺栓塞，并伴有内皮损伤。然而，DVT 的发病机制尚不清楚。凝血因子 XII（FXII）作为一种重要的凝血因子，据报道与血栓形成密切相关。然而，FXII 蛋白与 DVT 形成之间的关系尚未完全阐明。本研究探讨了 FXII 蛋白对 DVT 形成的影响，旨在揭示其潜在机制。
在本研究中，通过苏木精和伊红染色检查股静脉组织的组织学特征。通过 TUNEL 测定法检查股静脉组织损伤。通过 ELISA 检测超氧化物歧化酶（SOD）和丙二醛（MDA）浓度。通过 ELISA、免疫组化染色和 Western blot 分析测定肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-8 和磷酸肌醇 3-激酶（PI3K）/AKT 信号。
结果表明，与对照组或假手术组相比，DVT 小鼠的血栓形成、FXII 蛋白、细胞凋亡和 SOD 浓度降低，而 MDA 浓度升高。DVT 小鼠的 TNF-α、IL-6、IL-8 和 PI3K/AKT 信号也上调。此外，FXII 敲低显著上调 SOD 浓度，并下调 DVT 小鼠的血栓形成和细胞凋亡以及 MDA 浓度。FXII 敲低还显著下调 TNF-α、IL-6 和 IL-8 的蛋白表达以及 PI3K/AKT 信号的激活。此外，LY294002 预处理显著下调 DVT 小鼠的血栓形成和细胞凋亡以及 MDA 含量，而上调 SOD 浓度。LY294002 预处理还显著下调 TNF-α、IL-6 和 IL-8 的蛋白水平。
综上所述，本研究表明，FXII 蛋白通过激活 PI3K/AKT 信号通路诱导炎症反应，促进 DVT 的发生。因此，靶向 FXII 蛋白可能成为治疗 DVT 的一种潜在方法。
