Skip to main content
Log in

The anti-inflammatory properties of HDLs are impaired in gout

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Objective

We sought to determine whether high-density lipoprotein (HDL) function was altered in gout patients.

Research design and methods

The study included 95 gout patients and 68 healthy controls. The concentrations of interleukin (IL)-1β and IL-9 were measured by ELISA, and indicators such as blood uric acid, liver and kidney function, blood glucose, and blood lipids were detected. To test for the anti-inflammatory and reverse cholesterol transport (RCT) function of HDL, 11 gout patients and 11 healthy controls were randomly selected for the BioVision cholesterol efflux test, which detects the RCT activity of HDL. To assess the anti-inflammatory function of HDL, cells in co-culture with HDL were treated with inflammatory stimuli such as tumor necrosis factor-α (TNF-α), and then, the cells were assayed for the expression of intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecule-1 (VCAM-1).

Results

In total, this study enrolled 163 participants, including 95 non-hyperlipidemic gout patients and 68 healthy controls. IL-1β and IL-9 levels were significantly higher in the gout group than in the control group (85.26 ± 23.16 vs. 41.47 ± 6.48 and 33.77 ± 12.68 vs. 23.66 ± 4.53, respectively, P < 0.001). Additionally, plasma IL-1β and IL-9 levels were increased along with those of blood uric acid (R2 = 0.4116 and R2 = 0.4150, respectively, P < 0.001). Compared with the healthy controls, gout patients showed no differences in plasma apoA-1 levels or in the cholesterol efflux assay. Gout patients had increased ICAM-1 expression compared with the healthy controls (88.79 ± 3.68 vs. 86.27 ± 4.64, P < 0.05), but no difference in VCAM-1 expression was found (0.87 ± 0.43 vs. 0.98 ± 0.96, P > 0.05). In this assay, higher values indicate less suppression of ICAM-1 induction, which correlates with a reduced anti-inflammatory capacity.

Conclusions

The anti-inflammatory activities of HDLs are impaired in gout patients.

Key Points

• Gout patients show chronic inflammation.

• The anti-inflammatory activity of high-density lipoprotein is impaired in gout patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Barnett R (2018) Gout. Lancet 391(10140):2595

    Article  Google Scholar 

  2. Bevis M, Blagojevic-Bucknall M, Mallen C, Hider S, Roddy E (2018) Comorbidity clusters in people with gout: an observational cohort study with linked medical record review. Rheumatology (Oxford) 57(8):1358–1363

    Article  Google Scholar 

  3. Hsu T-W, Lee P-S, Nfor ON, Lee C-L, Chen P-H, Tantoh DM, Lin L-Y, Chou M-C, Lee Y-C, Liaw Y-P (2019) The interaction between sex and hyperlipidemia on gout risk is modulated by HLA-B polymorphic variants in adult Taiwanese. Genes (Basel) 10(3)

  4. Yü TF, Dorph DJ, Smith H (1978) Hyperlipidemia in primary gout. Semin Arthritis Rheum 7(4):233–244

    Article  Google Scholar 

  5. Elfishawi MM, Zleik N, Kvrgic Z, Michet CJ, Crowson CS, Matteson EL, Bongartz T (2018) The rising incidence of gout and the increasing burden of comorbidities: a population-based study over 20 years. J Rheumatol 45(4):574–579

    Article  Google Scholar 

  6. Heinecke JW (2009) The HDL proteome: a marker--and perhaps mediator--of coronary artery disease. J Lipid Res 50(Suppl):S167–S171

    Article  Google Scholar 

  7. Wang Y, Wang Z, Li X, Zhang B (2019) Correlation between serum apolipoprotein A1 and serum uric acid level in patients with hyperuricemia. Environ Dis 4(4):95–98

    Article  Google Scholar 

  8. Ouimet M, Barrett TJ, Fisher EA (2019) HDL and reverse cholesterol transport. Circ Res 124(10):1505–1518

    Article  CAS  Google Scholar 

  9. Meurs I, Van Eck M, Van Berkel TJC (2010) High-density lipoprotein: key molecule in cholesterol efflux and the prevention of atherosclerosis. Curr Pharm Des 16(13):1445–1467

    Article  CAS  Google Scholar 

  10. So AK, Martinon F (2017) Inflammation in gout: mechanisms and therapeutic targets. Nature reviews. Rheumatology 13(11):639–647

    CAS  PubMed  Google Scholar 

  11. Shridas P, De Beer MC, Webb NR (2018) High-density lipoprotein inhibits serum amyloid A-mediated reactive oxygen species generation and NLRP3 inflammasome activation. J Biol Chem 293(34):13257–13269

    Article  CAS  Google Scholar 

  12. Thacker SG, Zarzour A, Chen Y, Alcicek MS, Freeman LA, Sviridov DO, Demosky SJ, Remaley AT (2016) High-density lipoprotein reduces inflammation from cholesterol crystals by inhibiting inflammasome activation. Immunology 149(3):306–319

    Article  CAS  Google Scholar 

  13. Scanu A, Luisetto R, Oliviero F, Gruaz L, Sfriso P, Burger D, Punzi L (2015) High-density lipoproteins inhibit urate crystal-induced inflammation in mice. Ann Rheum Dis 74(3):587–594

    Article  CAS  Google Scholar 

  14. Hung AM, Tsuchida Y, Nowak KL, Sarkar S, Chonchol M, Whitfield V, Salas N, Dikalova A, Yancey PG, Huang J, Linton MRF, Ikizler TA, Kon V (2019) IL-1 inhibition and function of the HDL-containing fraction of plasma in patients with stages 3 to 5 CKD. Clin J Am Soc Nephrol 14(5):702–711

    Article  CAS  Google Scholar 

  15. Bresnihan B, Gogarty M, FitzGerald O, Dayer J-M, Burger D (2004) Apolipoprotein A-I infiltration in rheumatoid arthritis synovial tissue: a control mechanism of cytokine production? Arthritis Res Ther 6(6):R563–R566

    Article  CAS  Google Scholar 

  16. Duan L, Huang Y, Qun S, Lin Q, Liu W, Luo J, Yu B, He Y, Qian H, Liu Y, Chen J, Shi G (2016) Potential of IL-33 for preventing the kidney injury via regulating the lipid metabolism in gout patients. J Diabetes Res 2016:102–401

    Article  Google Scholar 

  17. Kristal BS, Vigneau-Callahan KE, Moskowitz AJ, Matson WR (1999) Purine catabolism: links to mitochondrial respiration and antioxidant defenses? Arch Biochem Biophys 370(1):22–33

    Article  CAS  Google Scholar 

  18. Lee-Rueckert M, Escola-Gil JC, Kovanen PT (2016) HDL functionality in reverse cholesterol transport - challenges in translating data emerging from mouse models to human disease. Biochim Biophys Acta 1861(7):566–583

    Article  CAS  Google Scholar 

  19. Tseng C-C, Chen C-J, Yen J-H, Huang H-Y, Chang J-G, Chang S-J, Liao W-T (2018) Next-generation sequencing profiling of mitochondrial genomes in gout. Arthritis Res Ther 20(1):137

  20. Cardona F, Tinahones FJ, Collantes E, Escudero A, García-Fuentes E, Soriguer FJ (2005) Contribution of polymorphisms in the apolipoprotein AI-CIII-AIV cluster to hyperlipidaemia in patients with gout. Ann Rheum Dis 64(1):85-88

  21. Fazio S, Pamir N (2016) HDL particle size and functional heterogeneity. Circ Res 119(6):704–707

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Yuan Wang and Yan Wang contributed to the study conception and design. Material preparation and data collection were performed by all authors. Data analysis and writing the first draft of the manuscript were performed by Yuan Wang; all authors commented on subsequent versions of the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Baoyu Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts 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

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Wang, Y., Jia, X. et al. The anti-inflammatory properties of HDLs are impaired in gout. Clin Rheumatol 40, 1525–1531 (2021). https://doi.org/10.1007/s10067-020-05374-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-020-05374-z

Keywords

Navigation