Aim  Assessment of the relationship between Wnt signaling pathway proteins (Wnt1 and Wnt3a) and matrix metalloproteinases (MMP-1, -9, -14) in patients with stable coronary artery disease (CAD) and various patterns of coronary artery involvement.

Material and methods  This cross-sectional study included 94 patients divided into two groups based on the severity of CA lesions as determined by coronary angiography or computer tomography angiography. Group 1 consisted of 32 patients with non-obstructive CAD (NOCAD, CA stenosis <50%), including 20 (62.5%) women, with a median age of 63.5 [55.3; 71.7] years and a BMI of 28.1 [23.7; 32.5] kg/m². Group 2 included 62 patients with obstructive CAD (OCAD, CA stenosis >50%), including 43 (69.4%) men, with a median age of 64.0 [55.2; 72.8] years and a BMI of 27.5 [23.2; 31.8] kg/m². All patients underwent standard laboratory and instrumental examinations. Plasma concentrations of Wnt1, Wnt3a, MMP-1, MMP-9, and MMP-14 were measured using enzyme-linked immunosorbent assay. Statistical analysis was performed using parametric and non-parametric methods, ROC analysis, and binary logistic regression.

Results  In patients with OCAD, concentrations of Wnt1, Wnt3a, and MMP-9 were significantly higher compared to the NOCAD group. MMP-9 concentrations were 7.20 (4.20-10.80) ng/mL in OCAD vs. 3.58 (1.95-6.47) ng/mL in NOCAD (p<0.001); Wnt1 was 0.19 (0.19-0.22) ng/mL and 0.15 (0.15-0.16) ng/mL, respectively (p<0.001); and Wnt3a was 0.23 (0.18-0.28) ng/mL compared to 0.11 (0.05-0.14) ng/mL (p<0.001). Significant positive correlations were found between the biomarkers MMP-9 and Wnt1 (r=0.449, p<0.001), and Wnt1 and Wnt3a (r=0.691, p<0.001). According to ROC analysis, Wnt1 demonstrated the highest diagnostic efficiency (AUC=0.975). A multivariate model including MMP-9, Wnt1, and Wnt3a showed a high predictive value (sensitivity 94.9%, specificity 95.2%).

Conclusion  This study is the first to demonstrate a statistically significant correlation between Wnt cascade markers (Wnt1, Wnt3a) and MMP-9 in patients with stable CAD across various CA lesion patterns. We observed a marked increase in plasma concentrations for MMP-9 (twofold), Wnt1 (1.3-fold), and Wnt3a (2.1-fold) in patients with OCAD. Consequently, the combination of Wnt and MMP-9 biomarkers may serve as a potential tool for differentiating between types of CA involvement.