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.
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.
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.
We demonstrated here that the thioredoxin-1 had atheroprotective functions through thioredoxin-1/NLRP3 inflammasome pathway.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
All data have been presented in the figures. And other related information are available under request to the corresponding author.
J. Frostegard, Immunity, atherosclerosis and cardiovascular disease. BMC Med. 11, 117 (2013)
J.Y. Xu et al. Therapeutic application of endothelial progenitor cells for treatment of cardiovascular diseases. Curr. Stem Cell Res. Ther. 9(5), 401–414 (2014)
C. Kasikara et al. The role of non-resolving inflammation in atherosclerosis. J. Clin. Invest. 128(7), 2713–2723 (2018)
I. Zeller, S. Srivastava, Macrophage functions in atherosclerosis. Circ. Res. 115(12), e83–e85 (2014)
I. Tabas, K.E. Bornfeldt, Macrophage phenotype and function in different stages of atherosclerosis. Circ. Res. 118(4), 653–667 (2016)
A. Grebe, F. Hoss, E. Latz, NLRP3 inflammasome and the IL-1 pathway in atherosclerosis. Circ. Res. 122(12), 1722–1740 (2018)
Z. Hoseini et al. NLRP3 inflammasome: its regulation and involvement in atherosclerosis. J. Cell. Physiol. 233(3), 2116–2132 (2018)
T. Karasawa, M. Takahashi, Role of NLRP3 inflammasomes in atherosclerosis. J. Atheroscler. Thromb. 24(5), 443–451 (2017)
R. Zhou et al. A role for mitochondria in NLRP3 inflammasome activation. Nature 469(7329), 221–225 (2011)
K. Schroder, R. Zhou, J. Tschopp, The NLRP3 inflammasome: a sensor for metabolic danger? Science 327(5963), 296–300 (2010)
M. Aviram, Atherosclerosis: cell biology and lipoproteins-inflammation and oxidative stress in atherogenesis: protective role for paraoxonases. Curr. Opin. Lipidol. 22(3), 243–244 (2011)
D. Harrison et al. Role of oxidative stress in atherosclerosis. Am. J. Cardiol. 91(3A), 7A–11A (2003)
J. Lu, A. Holmgren, The thioredoxin antioxidant system. Free Radic. Biol. Med. 66, 75–87 (2014)
G. Powis, W.R. Montfort, Properties and biological activities of thioredoxins. Annu. Rev. Biophys. Biomol. Struct. 30, 421–455 (2001)
G. Powis, W.R. Montfort, Properties and biological activities of thioredoxins. Annu. Rev. Pharmacol. Toxicol. 41, 261–295 (2001)
Z.A. Wood, L.B. Poole, P.A. Karplus, Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science 300(5619), 650–653 (2003)
S.I. Hashemy, A. Holmgren, Regulation of the catalytic activity and structure of human thioredoxin 1 via oxidation and S-nitrosylation of cysteine residues. J. Biol. Chem. 283(32), 21890–21898 (2008)
W.H. Watson et al. Redox potential of human thioredoxin 1 and identification of a second dithiol/disulfide motif. J. Biol. Chem. 278(35), 33408–33415 (2003)
C.H. Lillig, A. Holmgren, Thioredoxin and related molecules-from biology to health and disease. Antioxid. Redox Signal. 9(1), 25–47 (2007)
C.S. Pillay, J.H. Hofmeyr, J.M. Rohwer, The logic of kinetic regulation in the thioredoxin system. BMC Syst. Biol. 5, 15 (2011)
N. Kondo et al. Redox-sensing release of human thioredoxin from T lymphocytes with negative feedback loops. J. Immunol. 172(1), 442–448 (2004)
S. Miyamoto et al. Plasma thioredoxin levels and platelet aggregability in patients with acute myocardial infarction. Am. Heart J. 146(3), 465–471 (2003)
J. Hokamaki et al. Plasma thioredoxin levels in patients with unstable angina. Int. J. Cardiol. 99(2), 225–231 (2005)
A. Jekell et al. Elevated circulating levels of thioredoxin and stress in chronic heart failure. Eur. J. Heart. Fail. 6(7), 883–890 (2004)
P. Jakobs et al. Nuclear factor (erythroid-derived 2)-like 2 and thioredoxin-1 in atherosclerosis and ischemia/reperfusion injury in the heart. Antioxid. Redox Signal. 26(12), 630–644 (2017)
J. Madrigal-Matute et al. Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis. Free Radic. Biol. Med. 86, 352–361 (2015)
K. El Hadri et al. Thioredoxin-1 promotes anti-inflammatory macrophages of the M2 phenotype and antagonizes atherosclerosis. Arterioscler Thromb. Vasc. Biol. 32(6), 1445–1452 (2012)
B. Huang et al. Intravitreal injection of hydrogen peroxide induces acute retinal degeneration, apoptosis, and oxidative stress in mice. Oxid. Med. Cell. Longev. 2018, 5489476 (2018)
J.Y. Xu et al. Generation of induced cardiospheres via reprogramming of skin fibroblasts for myocardial regeneration. Stem Cells 34(11), 2693–2706 (2016)
This study was funded by Science Program of Yiwu, Zhejiang (Grant Number NO. 18-3-90).
Conflict of interest
The authors declare that they have no conflict of interest.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Wang, Y., Ji, N., Gong, X. et al. Thioredoxin-1 attenuates atherosclerosis development through inhibiting NLRP3 inflammasome. Endocrine (2020). https://doi.org/10.1007/s12020-020-02389-z