Transforming growth factor B₁ (TGF-β₁) expression correlates with phenotypic alterations in Chronic Venous Insufficiency (CVI)

The molecular mechanisms of CVI are poorly defined. We tested the hypothesis that TGF-β₁ gene expression is stimulated in CVI patients and may be responsible for wall abnormalities in varicose veins (VV). We obtained 10 VV and 7 normal veins (NV) from patients requiring surgery. Patients were separated into three groups according to CEAP classification: Group 1 (n=7, patients without CVI), Group 2 (n=4, CEAP 3 and 4) and Group 3 (n=5, CEAP class 5 and 6). Specimens were analyzed for TGF-β₁ gene expression by RT-PCR using glyceraldehyde-3-phosphate dehydrogenase (GAP) as a reference, and by electron microscopy for ultrastructural changes. TGF-β₁ mRNA was present in all VV (mean TGF-β₁/GAP ratio = 0.5 ± 0.2 SEM, p≤0.03), but was not detectable in NV. VV had largely increased collagen deposition and diffuse vein wall fibrosis relative to classical appearance of NV. Smooth muscle cells (SMC) appeared vacuolated in VV and were elliptical rather than spindle-shaped compared to NV. These data demonstrate that TGF-β₁ gene expression is increased in CVI and VV formation, and suggest that TGF-β₁ induces SMC transformation to an apparent secretory phenotype.