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

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.

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