Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.
Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho University.
J Toxicol Sci. 2021;46(4):187-192. doi: 10.2131/jts.46.187.
Tissue factor (TF) is the initiator of the coagulation cascade, constitutively expressed in subendothelial cells such as vascular smooth muscle cells and initiating rapid coagulation when the vascular vessel is damaged. TF has been shown to be involved in the development and progression of atherosclerosis. Arsenic, an environmental pollutant, is related to the progression of atherosclerosis, although the pathogenic mechanisms are not fully elucidated. In the present study, we investigated the effect of arsenite on the expression of TF in human aortic smooth muscle cells (HASMCs) and the underlying molecular mechanisms. We found that (1) arsenite stimulated TF synthesis and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in HASMCs, (2) sulforaphane, an Nrf2 activator, also stimulated TF synthesis in HASMCs, and (3) arsenite-induced upregulation of TF synthesis was prevented by Nrf2 knockdown in HASMCs. These results suggest that arsenite promotes TF synthesis by activating the Nrf2 pathway in HASMCs and that the induction of TF expression by arsenite may be related to the progression of atherosclerosis.
组织因子（TF）是凝血级联反应的启动子，在血管平滑肌细胞等血管内皮细胞中持续表达，在血管受损时迅速引发凝血。TF 已被证明参与动脉粥样硬化的发生和发展。砷是一种环境污染物，与动脉粥样硬化的进展有关，尽管其发病机制尚未完全阐明。在本研究中，我们研究了亚砷酸钠对人主动脉平滑肌细胞（HASMC）中 TF 表达的影响及其潜在的分子机制。我们发现：（1）亚砷酸钠刺激 TF 合成并激活 HASMC 中的核因子红细胞 2 相关因子 2（Nrf2）途径；（2）Nrf2 激活剂萝卜硫素也刺激 HASMC 中的 TF 合成；（3）Nrf2 敲低可防止 HASMC 中由亚砷酸钠诱导的 TF 合成上调。这些结果表明，亚砷酸钠通过激活 HASMC 中的 Nrf2 途径促进 TF 合成，亚砷酸钠诱导的 TF 表达可能与动脉粥样硬化的进展有关。
