Expression Profiling and Transcriptional Coordination of Canonical Wnt Signaling Pathway Genes (FZD2, DVL2, and AXIN1) in Chronic Venous Insufficiency

Background/Objectives: Chronic venous insufficiency (CVI) is a progressive vascular disorder characterized by sustained venous hypertension leading to structural and functional alterations of the venous wall. Despite its clinical significance, the molecular mechanisms driving venous remodeling remain incompletely understood. The Wnt signaling pathway has emerged as an important regulator of vascular homeostasis and remodeling; however, the expression and coordination of its core components in chronic venous insufficiency (CVI)-affected tissue have not been directly investigated. This study aimed to analyze mRNA expression of FZD2, DVL2, and AXIN1 in great saphenous vein specimens. In addition to gene expression analysis at the individual level, an investigation of co-regulatory networks was also performed to provide insight into Wnt cascade regulation in the varicose and healthy vein tissues. Methods: This single-center, retrospective observational study was conducted on 60 great saphenous vein specimens (32 CVI patients and 28 healthy controls) using re-al-time quantitative PCR. Results: The findings indicate that individual mRNA expression levels of FZD2, DVL2, and AXIN1 remained stable between varicose vein and healthy control tissues, but there were significant changes in transcriptional coordination among these genes in varicose vein tissues, especially enhanced co-expression between AXIN1 and DVL2. All three co-regulated genes exhibited moderate and generally comparable positive correlations in healthy controls: FZD2 with DVL2 (r = 0.526, p-value = 0.0069), DVL2 with AXIN1 (r = 0.486, p-value = 0.0161), and AXIN1 with FZD2 (r = 0.593, p-value = 0.0014). While in varicose vein tissues, DVL2-AXIN1 showed the highest correlation (r = 0.722, p-value < 0.0001), FZD2-DVL2 (r = 0.517, p-value = 0.0096) and AXIN1-FZD2 (r = 0.480, p-value = 0.0084) remained comparable to the healthy tissues. Conclusions: This finding indicates that the involvement of FZD2, DVL2, and AXIN1 in CVI may be driven by altered transcriptional coordination rather than by differential individual gene expression, which may contribute to the molecular pathology of chronic venous insufficiency.