Determination of the Association of Angiopoietin-Like Proteins with the Nature of Metabolic Abnormalities in Psoriatic Arthritis

Aim. To assess the prevalence of metabolic syndrome (MS) in patients with psoriatic arthritis (PsA) and to determine the associations of serum angiopoietin-like proteins (Angptl) of different types with the characteristics of metabolic disorders in this disease.

Design. Single-center cross-sectional clinical study.

Materials and methods. Forty-five patients older than 18 years with PsA (25 women and 20 men; mean age 47.5 ± 12.2 years; disease duration 7.9 ± 6.2 years) with predominantly high (DAS (Disease Activity Score) > 3.7) disease activity (67%) were examined. The presence of psoriasis was confirmed in 100% of cases, obesity of various severity was diagnosed in 17 people. Standard clinical and laboratory examination of all participants was supplemented by determination of serum Angptl of types 3, 4 and 6 by enzyme-linked immunosorbent assay.

Results. One-factor analysis of variance revealed no association between PsA activity and Angptl levels. MS according to the criteria of the International Diabetes Federation (IDF, 2006) was diagnosed in 27 (60%) patients with PsA. Intergroup comparison of Angptl indices of different types demonstrated an increased level of Angptl type 6 in the presence of MS (p = 0.018). Arterial hypertension was associated with high levels of type 6 Angptl in patients with PsA in the presence of MS. The content of Angptl types 3 and 6 was significantly higher in obese patients than in overweight patients (p = 0.002) and in PsA patients without obesity (p = 0.024).

Conclusion. Concentrations of serum Angptl types 3, 4 and 6 vary according to different metabolic phenotypes of PsA. Angptl types 3 and 6 can be used as diagnostic markers of metabolic disorders in PsA patients.

1. Pereverzina N.O., Kruglova L.S., Korotaeva T.V., Lila A.M. Systematic review and meta-analysis: risk factors for psoriatic arthritis. Part 2. Modern Rheumatology Journal. 2022;16(2):26–33. (in Russian). DOI: 10.14412/1996-7012-2022-2-26-33

2. Radner H., Lesperance T., Accortt N.A., Solomon D.H. Incidence and prevalence of cardiovascular risk factors among patients with rheumatoid arthritis, psoriasis, or psoriatic arthritis. Arthritis Care Res. (Hoboken). 2017;69(10):1510–8. DOI: 10.1002/acr.23171

3. Atzeni F., Gerratana E., Francesco Masala I., Bongiovanni S. et al. Psoriatic arthritis and metabolic syndrome: is there a role for disease modifying anti-rheumatic drugs? Front. Med. (Lausanne). 2021;8:735150. DOI: 10.3389/fmed.2021.735150

4. Labitigan M., Bahče-Altuntas A., Kremer J.M., Reed G. et al. Higher rates and clustering of abnormal lipids, obesity, and diabetes mellitus in psoriatic arthritis compared with rheumatoid arthritis. Arthritis Care Res. (Hoboken). 2014;66(4):600–7. DOI: 10.1002/acr.22185

5. Urruticoechea-Arana A., Castañeda S., Otón T., Benavent D. et al. Prevalence of metabolic syndrome in psoriatic arthritis: systematic literature review and results from the CARMA cohort. J. Clin. Rheumatol. 2022;28(2):e388–96. DOI: 10.1097/RHU.0000000000001738

6. Petcharat C., Srinonprasert V., Chiowchanwisawakit P. Association between syndesmophyte and metabolic syndrome in patients with psoriatic arthritis or ankylosing spondylitis: a cross-sectional study. BMC Musculoskelet. Disord. 2021;22(1):367. DOI: 10.1186/s12891-021-04222-8

7. Rodríguez-Zúñiga M.J.M., García-Perdomo H.A. Systematic review and meta-analysis of the association between psoriasis and metabolic syndrome. J. Am. Acad. Dermatol. 2017;77(4):657–66. e8. DOI: 10.1016/j.jaad.2017.04.1133

8. Kytikova O.Y., Antonyuk M.V., Kantur T.A., Novgorodtseva T.P. et al. Prevalence and biomarkers of metabolic syndrome. Obesity and Metabolism. 2021;18(3):302–12. (in Russian). DOI: 10.14341/omet12704

9. Alferova V.I., Mustafina S.V. Adipocytokines through the prism of human metabolic phenotypes. Doctor.Ru. 2023;22(4):18–23. (in Russian). DOI: 10.31550/1727-2378-2023-22-4-18-23

10. Chang J.S., Namkung J. Effects of exercise intervention on mitochondrial stress biomarkers in metabolic syndrome patients: a randomized controlled trial. Int. J. Environ. Res. Public Health. 2021;18(5):2242. DOI: 10.3390/ijerph18052242

11. Esfahani M., Baranchi M., Goodarzi M.T. The implication of hepatokines in metabolic syndrome. Diabetes Metab. Syndr. 2019;13(4):2477–80. DOI: 10.1016/j.dsx.2019.06.027

12. Masuko K. Angiopoietin-like 4: a molecular link between insulin resistance and rheumatoid arthritis. J. Orthop. Res. 2017;35(5):939–43. DOI: 10.1002/jor.23507

13. Aleksandrov A., Aleksandrov V., Shilova L. Study of the role of angiopoietin-like protein type 4 in metabolic disorders caused by inflammation in rheumatoid arthritis. Ann. Rheum. Dis. 2020;79(S1):1341. DOI: 10.1136/annrheumdis-2020-eular.4558

14. Bini S., D'Erasmo L., Di Costanzo A., Minicocci I. et al. The interplay between angiopoietin-like proteins and adipose tissue: another piece of the relationship between adiposopathy and cardiometabolic diseases? Int. J. Mol. Sci. 2021;22(2):742. DOI: 10.3390/ijms22020742

15. Aleksandrov V.A. Metabolic syndrome: prospects for the use of angiopoetin-like proteins type 3 and 4 for the diagnosis of metabolic disorders. Medical Council. 2023;17(16):68–75. (in Russian). DOI: 10.21518/ms2023-303

16. Namkung J., Sohn J.H., Chang J.S., Park S.W. et al. Increased serum angiopoietin-like 6 ahead of metabolic syndrome in a prospective cohort study. Diabetes Metab. J. 2019;43(4):521–9. DOI: 10.4093/dmj.2018.0080

17. Queiro R., Lorenzo A., Tejón P., Coto P. et al. Obesity in psoriatic arthritis: comparative prevalence and associated factors. Medicine (Baltimore). 2019;98(28):e16400. DOI: 10.1097/MD.0000000000016400

18. Abu-Farha M., Cherian P., Qaddoumi M.G., AlKhairi I. et al. Increased plasma and adipose tissue levels of ANGPTL8/Betatrophin and ANGPTL4 in people with hypertension. Lipids Health Dis. 2018;17(1):35. DOI: 10.1186/s12944-018-0681-0

19. Arab Sadeghabadi Z., Nourbakhsh M., Alaee M., Nourbakhsh M. et al. Angiopoietin-like proteins 2 and 3 in children and adolescents with obesity and their relationship with hypertension and metabolic syndrome. Int. J. Hypertens. 2021;2021:6748515. DOI: 10.1155/2021/6748515

20. Love T.J., Zhu Y., Zhang Y., Wall-Burns L. et al. Obesity and the risk of psoriatic arthritis: a population-based study. Ann. Rheum. Dis. 2012;71(8):1273–7. DOI: 10.1136/annrheumdis-2012-201299