Yu Wang1, Ningning Ji1, Xinyang Gong1, Shimao Ni1, Lei Xu1, Hui Zhang2. 1. Department of Cardiology, Yiwu Central Hospital, 519 Nanmen Street, Yiwu, 322000, Zhejiang, China. 2. Department of Cardiology, Yiwu Central Hospital, 519 Nanmen Street, Yiwu, 322000, Zhejiang, China. shuxiancui1840@163.com.
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.
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-1p10 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-1p10 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.
Authors: Pauline Puylaert; Melissa Van Praet; Frederik Vaes; Cédric H G Neutel; Lynn Roth; Pieter-Jan Guns; Guido R Y De Meyer; Wim Martinet Journal: Biomedicines Date: 2022-05-19