The role of Wnt signaling in development of coronary artery disease: WNT1 protein in patients with obstructive and non-obstructive coronary artery disease

Background The WNT signaling pathways, are involved in a variety of physiological processes. Recently studies have shown that β-Catenin Signaling and its protein variants (WNT1, WNT3a), plays an important role in the development and progression of coronary artery disease. WNT signaling can be considered as a potential target for the prevention and treatment of atherosclerosis. Therefore, in this research, we determined the level of these proteins and showed the factors influencing to development of atherosclerosis and the appearance of symptoms of CCS. Purpose To determine the levels of WNT1 protein in patients with obstructive and nonobstructive coronary artery disease. Method The study included 65 patients with stable coronary artery disease who were divided into 2 groups according to the results of coronary angiography / СТ-angiography. Group I: patients with ischemia without coronary artery obstruction (INOCA) (n = 23; average age 64.5 [58.25; 70.00]; 37.5% men; body mass index (BMI) 27.89 [25.54; 30.19] kg/m2). Group II: patients with obstructive coronary artery disease (n= 42; average age 63.0 [56.0; 71.0]; 67.1% men, BMI 27.30 [24.75; 29.81] kg/ m2). All patients underwent standard examination: laboratory tests, electrocardiogram, Echo-cardiogram, monitoring of blood pressure and ECG exercise tests. Additionally, WNT1 protein was determined in blood plasma by enzyme-linked immunosorbent assay on an Adaltis Personal Lab analyzer (Italy). Result WNT1 protein levels were significantly different between the studied groups (p < 0.001). The median WNT1 concentration in group II (0.19 [0.19; 0.21] ng/mL) was significantly higher than in group I (0.15 [0.15; 0.15] ng/mL). Correlation analysis revealed that, WNT1 had a high direct relationship with stenosis (%) (ρ = 0.764, p < 0.001). A 1 unit increase in WNT1 was associated with a 0.055% increase in the degree of stenosis. Statistically significant differences were found between groups for the presence of myocardial infarction, Group II was 4.176 times less likely to be free of myocardial infarction compared to Group I (p = 0.002). The results of the analysis revealed that, the levels of total cholesterol and low-density lipoprotein (LDL) were significantly higher in group I compared to group II (p < 0.001 and p = 0.002, respectively). Conclusion According to the data of this study, increased WNT1 levels were observed in patients with obstructive coronary artery disease. The strong direct correlation of WNT1 with the degree of vascular stenosis underlines its potential role in the development of atherosclerosis and other cardiovascular diseases. Unexpectedly high levels of total cholesterol and LDL in group I. Thus, the WNT signaling pathway may play a key role in the process of atherosclerotic plaque formation, highlighting its potential as a diagnostic biomarker and a target for the development of personalized treatment strategies.