Protective effect of rivaroxaban on arteriosclerosis obliterans in rats through modulation of the toll‑like receptor 4/NF‑κB signaling pathway

Lou,Xinjiang; Yu,Zhi; Yang,Xiaoxia; Chen,Jie

doi:10.3892/etm.2019.7726

Protective effect of rivaroxaban on arteriosclerosis obliterans in rats through modulation of the toll‑like receptor 4/NF‑κB signaling pathway

Authors:
- Xinjiang Lou
- Zhi Yu
- Xiaoxia Yang
- Jie Chen
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Affiliations: Department of Vascular Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China
Published online on: July 3, 2019 https://doi.org/10.3892/etm.2019.7726
Pages: 1619-1626
Copyright: © Lou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to explore the pharmacological role of rivaroxaban in rats with arteriosclerosis obliterans (ASO) and the potential mechanism of its action. A total of 60 adult male Sprague Dawley (weighing 210‑250 g) were randomly assigned into either the sham group, model group or Riv group. Rats in the sham group were fed a normal diet, whereas those in model group and Riv group were fed a high‑fat diet for 8 weeks. After establishment of the ASO model, rats in the Riv group were intragastrically administered 10 mg/kg rivaroxaban, whereas those in the sham group and the model group were administrated with the same volume of 0.9% saline for 4 weeks. At the end of animal procedures, a blood sample and the femoral artery of the rats were harvested. The results of the present study revealed that rats in the model group presented with an irregularly narrowed femoral artery lumen, disordered endothelial cells, internal elastic plates and smooth muscle cells. By comparison, the arterial wall structure and stenosis of the femoral artery of rats in Riv group recovered and all the pathological changes were alleviated after rivaroxaban treatment. Levels of total cholesterol, triglycerides and low‑density lipoproteins decreased, whereas the level of high‑density lipoproteins increased in the Riv group compared with the model group. Rivaroxaban treatment significantly reduced serum levels of interleukin‑1, tumor necrosis factor‑α and monocyte chemoattractant protein‑1 (MCP‑1), and increased the serum level of transforming growth factor‑β (TGF‑β). Rats in the Riv group had reduced expression of toll‑like receptor 4 (TLR4), NF‑κB and MCP‑1, and increased expression of TGF‑β in femoral artery tissues compared with the model group. Therefore rivaroxaban may have exerted its anti‑atherosclerotic effects by regulating the expression of genes in the TLR4/NF‑κB signaling pathway and the activation of the downstream molecules.

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