WNT Signaling Cascade Proteins and Structural and Functional State of The Vascular Bed in Patients With Various Phenotypes of Stable Ischemic Heart Disease

Kardiologiia. 2025 Mar 31;65(3):3-9. doi: 10.18087/cardio.2025.3.n2853.

ABSTRACT

Aim To evaluate the concentration of the WNT signaling cascade proteins (WNT1, -3a, -4, -5a) and the state of the vasculature by photoplethysmography (PPG) in patients with different phenotypes of stable ischemic heart disease (IHD), with obstructive and non-obstructive coronary artery disease (CAD).Material and methods This cross-sectional observational study included 80 patients (45-75 years old) with a verified diagnosis of stable IHD. Based on the results of coronary angiography or multislice spiral computed tomography coronary angiography, the patients were divided into two equal groups (n=40), with obstructive IHD (oIHD), and ischemia with no obstructive CAD or angina with no obstructive CAD (INOCA/ANOCA). In the oIHD group, men prevailed (67.5%) while in the INOCA/ANOCA group, women prevailed (57.5%). Noninvasive PPG evaluation of the vasculature was performed, and WNT1, -3a, -4, and -5a concentrations were measured by ELISA in all patients.Results Higher concentrations of the WNT1 and WNT3a proteins were found in patients with oIHD (p<0.001) while the INOCA/ANOCA group had a significantly higher concentration of WNT5a (p=0.001). According to the PPG data, the arterial stiffness index (aSI) significantly differed between the INOCA/ANOCA (7.6 m/s [6.6; 9.35]) and oIHD (9.25 m/s [7.88; 10.33]) groups, p=0.048). The correlation analysis revealed a relationship between WNT1 and the reflectance index RI (ρ=0.359; p=0.014) in IHD patients (oIHD+INOCA/ANOCA). According to the ROC analysis, the curve for WNT3a turned out to be diagnostically significant (sensitivity and specificity of the model were 85.7 and 87.0%, respectively). The cut-off value of WNT3a was 0.183 pg/ml.Conclusion The results of the study showed that the activation of the canonical WNT cascade (WNT1 and WNT3a) was observed in patients with oIHD, while the non-canonical cascade (WNT5a) was activated in patients with INOCA/ANOCA. The obstructive IHD phenotype can be predicted with a WNT3a value ≥0.183 pg/ml.

PMID:40195773 | DOI:10.18087/cardio.2025.3.n2853