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Assessment of Wnt1 and Wnt3a levels in patients with different phenotypes of stable coronary artery disease

https://doi.org/10.20996/1819-6446-2025-3229

EDN: RJNNIQ

Abstract

Aim. To assess the Wnt1 and Wnt3a proteins levels in patients with stable coronary artery disease (CAD) and different phenotypes of coronary artery lesions.
Material and methods. A cross-sectional study included 72 patients with a verified diagnosis of stable CAD (aged 45-75 years) and 30 healthy individuals (control group) without cardiovascular risk factors. Based on coronary angiography or multispiral computed tomography, patients were divided into two groups. Group I — with non-obstructive coronary artery lesions (non-obCAD, n=30; including 11 men (37.5%); median age — 66.0 years [60.5; 71.5]; body mass index (BMI) 26.7 [25.5-30.2] kg/m²); Group II — with obstructive coronary artery lesions (obCAD, n=42; including 30 men (71.4%); median age — 64.0 years [57.0; 72.0]; BMI 27.4; [24.8; 29.8] kg/m²). The control group included 30 volunteers (10 men (33.3%); median age — 28.0 years [26.0; 37.0]; BMI 22.0; [20.9; 25.3] kg/m²). All patients underwent standard laboratory testing (complete blood count, biochemistry blood test, urinalysis) and instrumental diagnostics: electrocardiography (ECG), 24-hour Holter ECG monitoring, echocardiography, stress echocardiography and/or myocardial perfusion scintigraphy with a stress test. The levels of Wnt1 and Wnt3a proteins, endothelin-1, interleukins (IL-1β, IL-6), and C-reactive protein were determined by enzyme-linked immunosorbent assay.
Results. The CAD patient groups were comparable in age and BMI but differed in sex: the obstructive CAD group was predominantly male (71.4%), while females predominated (62.5%) in the non-obstructive CAD group. The level of Wnt1 protein was significantly higher in the obstructive CAD group (0.19 ng/ml) compared to both the non-obstructive CAD (0.15 ng/ml; p<0.001) and control groups (0.15 ng/ml; p=0.001). The level of Wnt3a was also higher in the obstructive CAD group (0.24 ng/ml) and the control group (0.25 ng/ml) than in the non-obstructive CAD group (0.11 ng/ml; p<0.001). Endothelin-1 levels were higher in the nonobstructive CAD group (33.5 pg/ml) than in the obstructive CAD group (27.3 pg/ml; p=0.027). Inflammatory markers (IL-1β, IL-6, CRP) did not differ significantly. Factor analysis revealed two main components: “lipid profile” and “endothelial damage” (Wnt1, Wnt3a, and endothelin-1). ROC analysis showed the second component had high prognostic ability for differentiating CAD phenotypes (AUC=0.987; p<0.001). A logistic regression model based on Wnt1 and Wnt3a demonstrated high accuracy (AUC=0.953) in identifying obstructive CAD.
Conclusion. The obtained data may suggest a possible role of the Wnt signaling pathway in the pathogenesis of different types of coronary artery lesions in CAD. Increased levels of Wnt1 and Wnt3a were associated with obstructive coronary artery lesions. An attempt was made to develop a regression model based on Wnt1 and Wnt3a concentrations. The resulting model has high diagnostic value for identifying patients with obCAD. This allows considering these proteins as potential prognostic biomarkers for risk stratification and clarifying the type of coronary artery lesion in CAD.

About the Authors

M. Al-Ahdal
Sechenov First Moscow State Medical University
Russian Federation

Mustafa Al-Ahdal

Moscow



A. O. Iusupova
Sechenov First Moscow State Medical University
Russian Federation

Alfiya O. Iusupova

Moscow



N. N. Pakhtusov
Sechenov First Moscow State Medical University
Russian Federation

Nikolay N. Pakhtusov

Moscow



O. A. Slepova
Sechenov First Moscow State Medical University
Russian Federation

Olga A. Slepova

Moscow



A. S. Lishuta
Sechenov First Moscow State Medical University
Russian Federation

Alexey S. Lishuta

Moscow



Yu. N. Belenkov
Sechenov First Moscow State Medical University
Russian Federation

Yuri N. Belenkov

Moscow



References

1. Nusse R, Clevers H. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell. 2017;169(6):985–999. doi: 10.1016/j.cell.2017.05.016.

2. Foulquier S, Daskalopoulos EP, Lluri G, Hermans KCM, Deb A, Blankesteijn WM. WNT Signaling in Cardiac and Vascular Disease. Pharmacol Rev. 2018;70(1):68–141. doi: 10.1124/pr.117.013896.

3. Katoh M, Katoh M. WNT signaling pathway and stem cell signaling network. Clin Cancer Res. 2007;13(14):4042–4045. doi: 10.1158/1078-0432.CCR-06-2316.

4. Cadigan KM, Nusse R. Wnt signaling: a common theme in animal development. Genes Dev. 1997;11(24):3286–3305. doi: 10.1101/gad.11.24.3286.

5. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004; 20:781–810. doi: 10.1146/annurev.cellbio.20.010403.113126.

6. Khan K, Yu B, Tardif J-C, Rhéaume E, Al-Kindi H, Filimon S, Pop C, Genest J, Cecere R, Schwertani A. Significance of the Wnt signaling pathway in coronary artery atherosclerosis. Front Cardiovasc Med. 2024; 11:1360380. Doi: 10.3389/fcvm.2024.1360380.

7. Weerackoon N, Gunawardhana KL, Mani A. Wnt signaling cascades and their role in coronary artery health and disease. J Cell Signal. 2021;2(1):52–62. doi: 10.33696/Signaling.2.035

8. Mill C, George SJ. Wnt signaling in smooth muscle cells and its role in cardiovascular disorders. Cardiovasc Res. 2012;95(2):233–240. doi: 10.1093/cvr/cvs141.

9. Riascos-Bernal DF et al. Inhibition of smooth muscle β-catenin hinders neointima formation. Arteriosclerosis Thromb Vasc Biol. 2017;37(3):543–552. doi: 10.1161/ATVBAHA.116.308643.

10. Brown BA et al. Aging differentially modulates the Wnt pro-survival signaling pathways in vascular smooth muscle cells. Aging Cell. 2019;18(1): e12844. doi: 10.1111/acel.12844.

11. Golestaneh N et al. Wnt signaling promotes proliferation and stemness regulation of spermatogonial stem/progenitor cells. Reproduction. 2009;138(1):151–162. doi: 10.1530/REP-08-0510.

12. Malekar P et al. Wnt signaling is critical for maladaptive cardiac hypertrophy and accelerates myocardial remodeling. Hypertension. 2010;55(4):939–945. doi: 10.1161/HYPERTENSIONAHA.109.141127.

13. Liu Y., Neogi A., Mani A. The role of Wnt signaling in development of coronary artery disease and its risk factors. Open Biology, 2020, 10: 200128. doi: 10.1098/rsob.200128.

14. Khan K., Yu B., Tardif J.-C., et al. Significance of the Wnt signaling pathway in coronary artery atherosclerosis. Frontiers in Cardiovascular Medicine, 2024, 11: 1360380. doi:10.3389/fcvm.2024.1360380.

15. Naya, M., Aikawa, T., Manabe, O. et al. Elevated serum endothelin-1 is an independent predictor of coronary microvascular dysfunction in non-obstructive territories in patients with coronary artery disease. Heart Vessels 36, 917–923 (2021). https://doi.org/10.1007/s00380-020-01767-x.

16. Afroz R, Goodwin JE. Wnt Signaling in Atherosclerosis: Mechanisms to Therapeutic Implications. Biomedicines. 2024;12(2):276. doi:10.3390/biomedicines12020276.

17. Daskalopoulos EP, Blankesteijn WM. Effect of Interventions in WNT Signaling on Healing of Cardiac Injury: A Systematic Review. Cells. 2021;10(2):207. doi:10.3390/cells10020207.

18. Poznyak AV, Sukhorukov VN, Popov MA, Chegodaev YS, Postnov AY, Orekhov AN. Mechanisms of the Wnt Pathways as a Potential Target Pathway in Atherosclerosis. J Lipid Atheroscler. 2023;12(3):223–236. doi:10.12997/jla.2023.12.3.223.

19. Svetláková BB, Líšková VP, Barančík M. Wnt Signaling Inhibitors as Therapeutic Approach in Ischemic Heart Disease. Molecules. 2024;29(24):5958. doi:10.3390/molecules29245958.

20. Pepine C. J. ANOCA/INOCA/MINOCA: Open artery ischemia. American Heart Journal Plus: Cardiology Research and Practice, 2023, 26: 100260. doi: 10.1016/j.ahjo.2023.100260.


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Al-Ahdal M., Iusupova A.O., Pakhtusov N.N., Slepova O.A., Lishuta A.S., Belenkov Yu.N. Assessment of Wnt1 and Wnt3a levels in patients with different phenotypes of stable coronary artery disease. Rational Pharmacotherapy in Cardiology. 2025;21(5):433-440. (In Russ.) https://doi.org/10.20996/1819-6446-2025-3229. EDN: RJNNIQ

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)