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Article

Arsenite Inhibits Tissue-Type Plasminogen Activator Synthesis through NRF2 Activation in Cultured Human Vascular Endothelial EA.hy926 Cells

1
Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji 192-0392, Japan
2
Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi 274-8510, Japan
3
Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 739; https://doi.org/10.3390/ijms22020739
Received: 14 December 2020 / Revised: 5 January 2021 / Accepted: 9 January 2021 / Published: 13 January 2021
(This article belongs to the Special Issue Vascular Endothelial Cells 2.0)
Chronic arsenic exposure is known to be related to the progression of atherosclerosis. However, the pathogenic mechanisms of arsenic-induced atherosclerosis have not been fully elucidated. Because disruption of the blood coagulation/fibrinolytic system is involved in the development of arteriosclerosis, we investigated the effect of arsenite on fibrinolytic activity in human vascular endothelial EA.hy926 cells in the present study. Fibrinolysis depends on the balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) secreted from vascular endothelial cells. We found that arsenite reduced fibrinolytic t-PA activity by inhibiting its synthesis without affecting PAI-1 production. The inhibitory effect of arsenite on t-PA expression was partially recovered by the reactive oxygen species (ROS) scavenger Trolox. The nuclear factor erythroid 2 related factor 2 (NRF2) pathway is known to be activated by arsenite via ROS production. We confirmed that arsenite activated the NRF2 pathway, and arsenite-induced inhibition of fibrinolytic t-PA activity was abrogated in NRF2-knockdown EA.hy926 cells. These results suggest that arsenite inhibits the fibrinolytic activity of t-PA by selectively suppressing its synthesis via activation of the NRF2 pathway in vascular endothelial cells. View Full-Text
Keywords: arsenite; nuclear factor erythroid 2 related factor 2; tissue-type plasminogen activator; fibrinolysis; endothelial cell; atherosclerosis arsenite; nuclear factor erythroid 2 related factor 2; tissue-type plasminogen activator; fibrinolysis; endothelial cell; atherosclerosis
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MDPI and ACS Style

Nakano, T.; Takahashi, T.; Yamamoto, C.; Yoshida, E.; Kaji, T.; Fujiwara, Y. Arsenite Inhibits Tissue-Type Plasminogen Activator Synthesis through NRF2 Activation in Cultured Human Vascular Endothelial EA.hy926 Cells. Int. J. Mol. Sci. 2021, 22, 739. https://doi.org/10.3390/ijms22020739

AMA Style

Nakano T, Takahashi T, Yamamoto C, Yoshida E, Kaji T, Fujiwara Y. Arsenite Inhibits Tissue-Type Plasminogen Activator Synthesis through NRF2 Activation in Cultured Human Vascular Endothelial EA.hy926 Cells. International Journal of Molecular Sciences. 2021; 22(2):739. https://doi.org/10.3390/ijms22020739

Chicago/Turabian Style

Nakano, Tsuyoshi, Tsutomu Takahashi, Chika Yamamoto, Eiko Yoshida, Toshiyuki Kaji, and Yasuyuki Fujiwara. 2021. "Arsenite Inhibits Tissue-Type Plasminogen Activator Synthesis through NRF2 Activation in Cultured Human Vascular Endothelial EA.hy926 Cells" International Journal of Molecular Sciences 22, no. 2: 739. https://doi.org/10.3390/ijms22020739

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