Thioredoxin-1 attenuates atherosclerosis development through inhibiting NLRP3 inflammasome



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.

Fig. 1
Fig. 2
Fig. 3

Data availability

All data have been presented in the figures. And other related information are available under request to the corresponding author.


  1. 1.

    J. Frostegard, Immunity, atherosclerosis and cardiovascular disease. BMC Med. 11, 117 (2013)

    Article  Google Scholar 

  2. 2.

    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)

    CAS  Article  Google Scholar 

  3. 3.

    C. Kasikara et al. The role of non-resolving inflammation in atherosclerosis. J. Clin. Invest. 128(7), 2713–2723 (2018)

    Article  Google Scholar 

  4. 4.

    I. Zeller, S. Srivastava, Macrophage functions in atherosclerosis. Circ. Res. 115(12), e83–e85 (2014)

    CAS  Article  Google Scholar 

  5. 5.

    I. Tabas, K.E. Bornfeldt, Macrophage phenotype and function in different stages of atherosclerosis. Circ. Res. 118(4), 653–667 (2016)

    CAS  Article  Google Scholar 

  6. 6.

    A. Grebe, F. Hoss, E. Latz, NLRP3 inflammasome and the IL-1 pathway in atherosclerosis. Circ. Res. 122(12), 1722–1740 (2018)

    CAS  Article  Google Scholar 

  7. 7.

    Z. Hoseini et al. NLRP3 inflammasome: its regulation and involvement in atherosclerosis. J. Cell. Physiol. 233(3), 2116–2132 (2018)

    CAS  Article  Google Scholar 

  8. 8.

    T. Karasawa, M. Takahashi, Role of NLRP3 inflammasomes in atherosclerosis. J. Atheroscler. Thromb. 24(5), 443–451 (2017)

    CAS  Article  Google Scholar 

  9. 9.

    R. Zhou et al. A role for mitochondria in NLRP3 inflammasome activation. Nature 469(7329), 221–225 (2011)

    CAS  Article  Google Scholar 

  10. 10.

    K. Schroder, R. Zhou, J. Tschopp, The NLRP3 inflammasome: a sensor for metabolic danger? Science 327(5963), 296–300 (2010)

    CAS  Article  Google Scholar 

  11. 11.

    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)

    CAS  Article  Google Scholar 

  12. 12.

    D. Harrison et al. Role of oxidative stress in atherosclerosis. Am. J. Cardiol. 91(3A), 7A–11A (2003)

    CAS  Article  Google Scholar 

  13. 13.

    J. Lu, A. Holmgren, The thioredoxin antioxidant system. Free Radic. Biol. Med. 66, 75–87 (2014)

    CAS  Article  Google Scholar 

  14. 14.

    G. Powis, W.R. Montfort, Properties and biological activities of thioredoxins. Annu. Rev. Biophys. Biomol. Struct. 30, 421–455 (2001)

    CAS  Article  Google Scholar 

  15. 15.

    G. Powis, W.R. Montfort, Properties and biological activities of thioredoxins. Annu. Rev. Pharmacol. Toxicol. 41, 261–295 (2001)

    CAS  Article  Google Scholar 

  16. 16.

    Z.A. Wood, L.B. Poole, P.A. Karplus, Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science 300(5619), 650–653 (2003)

    CAS  Article  Google Scholar 

  17. 17.

    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)

    CAS  Article  Google Scholar 

  18. 18.

    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)

    CAS  Article  Google Scholar 

  19. 19.

    C.H. Lillig, A. Holmgren, Thioredoxin and related molecules-from biology to health and disease. Antioxid. Redox Signal. 9(1), 25–47 (2007)

    CAS  Article  Google Scholar 

  20. 20.

    C.S. Pillay, J.H. Hofmeyr, J.M. Rohwer, The logic of kinetic regulation in the thioredoxin system. BMC Syst. Biol. 5, 15 (2011)

    CAS  Article  Google Scholar 

  21. 21.

    N. Kondo et al. Redox-sensing release of human thioredoxin from T lymphocytes with negative feedback loops. J. Immunol. 172(1), 442–448 (2004)

    CAS  Article  Google Scholar 

  22. 22.

    S. Miyamoto et al. Plasma thioredoxin levels and platelet aggregability in patients with acute myocardial infarction. Am. Heart J. 146(3), 465–471 (2003)

    CAS  Article  Google Scholar 

  23. 23.

    J. Hokamaki et al. Plasma thioredoxin levels in patients with unstable angina. Int. J. Cardiol. 99(2), 225–231 (2005)

    Article  Google Scholar 

  24. 24.

    A. Jekell et al. Elevated circulating levels of thioredoxin and stress in chronic heart failure. Eur. J. Heart. Fail. 6(7), 883–890 (2004)

    CAS  Article  Google Scholar 

  25. 25.

    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)

    CAS  Article  Google Scholar 

  26. 26.

    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)

    CAS  Article  Google Scholar 

  27. 27.

    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)

    CAS  Article  Google Scholar 

  28. 28.

    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)

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    J.Y. Xu et al. Generation of induced cardiospheres via reprogramming of skin fibroblasts for myocardial regeneration. Stem Cells 34(11), 2693–2706 (2016)

    CAS  Article  Google Scholar 

Download references


This study was funded by Science Program of Yiwu, Zhejiang (Grant Number NO. 18-3-90).

Author information



Corresponding author

Correspondence to Hui Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Ji, N., Gong, X. et al. Thioredoxin-1 attenuates atherosclerosis development through inhibiting NLRP3 inflammasome. Endocrine (2020).

Download citation


  • Thioredoxin-1
  • Trx-1
  • Atherosclerosis
  • NLRP3