Thioredoxin-1 attenuates atherosclerosis development through inhibiting NLRP3 inflammasome
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ORIGINAL ARTICLE
Thioredoxin-1 attenuates atherosclerosis development through inhibiting NLRP3 inflammasome Yu Wang1 Ningning Ji1 Xinyang Gong1 Shimao Ni1 Lei Xu1 Hui Zhang ●
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Received: 7 April 2020 / Accepted: 10 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Backgrounds The thioredoxin-1 has atheroprotective effects via regulating oxidative stress and inflammation. In addition, the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome also contributes to atherosclerosis development. However, whether the thioredoxin-1 suppresses atherosclerosis development by modulating the NLRP3 inflammasome remains unclear. Methods The regulation of NLRP3 inflammasome by thioredoxin-1 was determined in vitro on macrophage cells after ox-LDL (oxidized low-density lipoprotein) stimulation. The IL-1β and caspase-1 p10 secretion were assessed by ELISA and western blot. Finally, the thioredoxin-1/NLRP3 inflammasome pathway was confirmed in apolipoprotein E-deficient mice. Results Thioredoxin-1 suppressed the expression of NLRP3, the secretion of IL-1β and caspase-1 p10 in vitro. And ROS stimulation activated the NLRP3 inflammasome which was inhibited by thioredoxin-1. In the mouse model of atherosclerosis, thioredoxin-1 delivered by lentivirus vector inhibited atherosclerosis development. And the atheroprotective effects of thioredoxin-1 were attenuated by ROS stimulation. Furthermore, the regulation of NLRP3 inflammasome by thioredoxin-1 was also confirmed in vivo. Conclusions We demonstrated here that the thioredoxin-1 had atheroprotective functions through thioredoxin-1/NLRP3 inflammasome pathway. Keywords Thioredoxin-1 Trx-1 Atherosclerosis NLRP3 ●
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Introduction Cardiovascular diseases are the most predominant diseases in the world with high mortality and morbidity [1–3]. Atherosclerosis, which has been characterized as an inflammatory disease, is the most important contributor to the development of cardiovascular diseases [1–3]. During atherosclerosis development, the low-density lipoproteins (LDL) are oxidized by ROS (reactive oxygen species) and promote the secretion of pro-inflammatory cytokines [4, 5]. Thus, targeting inflammation and oxidative stress might be a promising strategy for atherosclerosis treatment. Indeed, it has been demonstrated that inhibiting the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin
* Hui Zhang [email protected] 1
Department of Cardiology, Yiwu Central Hospital, 519 Nanmen Street, Yiwu, 322000 Zhejiang, China
domain-containing-3) inflammasome shows potential therapeutic effects on atherosclerosis [6]. The NLRP3 inflammasome plays an important role in inflammation stimulation and regulation [7, 8]. And this protein complex is consisted of NLRP3, caspase-1 and ASC (apoptosis-associated speck-like protein containing a caspase-1 recruitment domain) [9]. During the NLRP3 inflammasome activation, the NLRP3 protein is firstly activated. And the activated NLRP3 induces the activation of caspas
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