TGF-β1 Upregulation in the Aging Varicose Vein

Abstract

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-beta(1) 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-beta(1) examining the latent/mature form of TGF-beta(1) and the presence of mast cells. Effects of age were also evaluated. Saphenous veins were obtained from patients subjected to aortocoronary bypass (controls) and undergoing varicose vein surgery. These were immunolabeled using anti-LAP TGF-beta(1)/anti-TGF-beta(1) antibodies and subjected to Western blot. Mast cell population was identified by metachromatic staining. Latent TGF-beta(1) was significantly reduced in varicose veins from older subjects. In contrast, smooth muscle cells obtained from the varicosities showed intense levels. Mature TGF-beta(1) significantly differed between healthy and varicose veins. No mature TGF-beta(1) 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-beta(1). Aging and varicose pathology induce dysregulation of TGF-beta(1) that could play an important role in the fibrous process, representing the final stages of venous insufficiency.