Transcriptomic profiling of varicose veins and associated blood biomarkers

Background: Intervention for patients with symptomatic varicose veins is largely driven by a combination of symptoms, the magnitude of venous reflux, clinical severity scoring algorithms, and unresponsiveness to conservative medical therapy. Our goal was to evaluate biological features of superficial veins from patients with symptomatic varicose veins, comparing these to healthy veins for biological insight into the progression of superficial vein disease. Methods: RNA was extracted from incompetent great saphenous veins at the time of phlebectomy and compared with residual healthy superficial veins from patients following coronary artery bypass graft surgery. The venous wall transcriptome was interrogated by NanoString. PANTHER and Gene Ontology identified biological pathways of interest. Based on these data, plasma biomarkers from patients with varicose veins or matched controls were evaluated. Results: Multiple genes were upregulated and downregulated for pathways involving angiogenesis, collagen biosynthesis, and inflammation. COL1A1 was upregulated in varicose veins by fourfold, and interleukin-6 ( IL-6 ) was downregulated by 21-fold. The blood IL-6 concentration was higher in the validation cohort of patients with varicose veins compared with relatively healthy patients (4.8 vs 1.3 pg/mL, p = 0.0085). Blood collagen 1A1 (COL1A1) was lower in patients with varicose veins compared with healthy patients (66,355 vs 82,661 pg/mL, p = 0.0497). A positive association was observed between circulating COL1A1 concentration and the Venous Clinical Severity Score, suggesting its potential utility as a prognostic biomarker for pathological great saphenous vein remodeling in patients with varicose veins. Conclusions: This hypothesis-generating study revealed that blood COL1A1 and IL-6 concentrations may be blood biomarkers used as additional objective data that may indicate adverse vein remodeling in patients with varicose veins.