TGF-β₁ Upregulation in the Aging Varicose Vein

Abstract

Background: Although the etiology of venous insufficiency is not well understood, immune response and aging are beginning to emerge as contributing factors. Factors involved in tissue remodeling such as TGF-β₁ also seem to play an important role in extracellular matrix production. The aim of this study was to explore the relationship between chronic venous insufficiency and TGF-β₁ examining the latent/mature form of TGF-β₁ and the presence of mast cells. Effects of age were also evaluated. Methods: Saphenous veins were obtained from patients subjected to aortocoronary bypass (controls) and undergoing varicose vein surgery. These were immunolabeled using anti-LAP TGF-β₁/anti-TGF-β₁ antibodies and subjected to Western blot. Mast cell population was identified by metachromatic staining.Results:Latent TGF-β₁ was significantly reduced in varicose veins from older subjects. In contrast, smooth muscle cells obtained from the varicosities showed intense levels. Mature TGF-β₁ significantly differed between healthy and varicose veins. No mature TGF-β₁ was detected in the cell cultures. Mast cell number and degranulation were increased with aging and varicose disease, colocalizing with the mature form of TGF-β₁. Conclusion: Aging and varicose pathology induce dysregulation of TGF-β₁ that could play an important role in the fibrous process, representing the final stages of venous insufficiency.

Influence of thrombophlebitis on TGF-β1 and its signaling pathway in the vein wall.

“…Furthermore, these results are in accordance with those reported by Pascual et al [19], who demonstrated decreased protein expression of latent TGF-β1 in varicose veins of age-matched control and study groups with mean ages of 50 or over. However, when comparing varicose veins and varicose veins complicated by thrombophlebitis, a significant increase in active TGF-β1 expression was demonstrated in the course of thrombophlebitis.…”

“…Unchanged TGF-β1 levels in cell cultures from varicose veins and a comparable amount of the active form of TGF-β1 in the walls of varicose veins were demonstrated in some studies [15,16]. By contrast, increases in TGF-β1 mRNA levels, protein expression, immunostaining, and total content in the walls of varicose veins were reported in others [15,17,18], and decreased protein expression of the TGF-β1 latent form was demonstrated in the walls of varicose veins in an older group of patients [19].…”

“…TGF-β1 exerts a profound effect on the synthesis and degradation of a large number of ECM components [10]. However, ECM undergoes physiological changes with age, including TGF-β1 expression in vein walls [19,25]. Thus, to avoid age-related and individual differences between studied and control groups, we decided to assess TGF-β1 in normal and varicose veins harvested from the same patients with chronic venous insufficiency (CVI) symptoms.…”

“…Furthermore, Badier-Commander et al compared normal veins and varicose veins from subjects 15 years younger than the control group. Due to the decrease of latent TGF-β1 in walls of varicose veins with age, the age differences between studied and control groups should be considered when comparing these results [19].…”

Alternative Splicing in Endothelial Senescence: Role of the TGF-β Co-Receptor Endoglin

“…In the vascular context, it has been reported, e. g., elevated levels of TGF-in the aging varicose veins that likely favour the fibrous process and the consequent venous insufficiency (Pascual et al, 2007). In this sense, the profibrotic effect of TGF-is mediated by the stimulation via Smad3 signalling of the plasminogen activator inhibitor (PAI)-1 expression, a key regulator of the synthesis and deposition of the extracellular matrix in the tissue homeostasis (Ghosh & Vaughan, 2011).…”