Thioredoxin-1 Attenuates Atherosclerosis Development Through Inhibiting NLRP3 Inflammasome
Overview
Affiliations
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.
Cao R, Zhou J, Liu J, Wang Y, Dai Y, Jiang Y Inflammation. 2025; .
PMID: 40085192 DOI: 10.1007/s10753-025-02282-9.
A new model and precious tool to study molecular mechanisms of macrophage aging.
Smith R, Bassand K, Dussol A, Piesse C, Duplus E, El Hadri K Aging (Albany NY). 2024; 16(19):12697-12725.
PMID: 39373702 PMC: 11501386. DOI: 10.18632/aging.206124.
Oxidative Stress, Atherogenic Dyslipidemia, and Cardiovascular Risk.
Vekic J, Stromsnes K, Mazzalai S, Zeljkovic A, Rizzo M, Gambini J Biomedicines. 2023; 11(11).
PMID: 38001900 PMC: 10669174. DOI: 10.3390/biomedicines11112897.
Structural basis for thioredoxin-mediated suppression of NLRP1 inflammasome.
Zhang Z, Shibata T, Fujimura A, Kitaura J, Miyake K, Ohto U Nature. 2023; 622(7981):188-194.
PMID: 37704723 DOI: 10.1038/s41586-023-06532-4.
Thioredoxin-1 promotes the restoration of alveolar bone in periodontitis with diabetes.
Wu J, Huang Y, Zhan C, Chen L, Lin Z, Song Z iScience. 2023; 26(9):107618.
PMID: 37664614 PMC: 10470393. DOI: 10.1016/j.isci.2023.107618.