Effect of TGF-beta1 on MMP/TIMP and TGF-beta1 receptors in great saphenous veins and its significance on chronic venous insufficiency

Phlebology. 2017 Jun;32(5):334-341. doi: 10.1177/0268355516655067. Epub 2016 Jun 20.

Abstract

Objectives Transforming growth factor-beta1 (TGF-β1) may participate in local chronic inflammatory processes in varicose veins and in venous wall structure modifications through regulation of matrix metalloproteinases (MMP) and their inhibitors (tissue inhibitor of metalloproteinase (TIMP)). The aim of this study was to analyze the effect of TGF-β1 in the vein wall, namely on the gene expression of selected MMP, TIMP and TGF-β1 receptors. Methods Healthy vein samples were harvested from eight subjects who underwent coronary bypass graft surgery with great saphenous vein. Each vein sample was divided into two segments, which were cultivated separately in vitro (one of the segments had TGF-β1 added) and then submitted to gene expression analysis. Results In the TGF-β1 supplemented group, there was a general increase in the mean gene expression. Specifically, expression of MMP9, MMP12, TIMP1 and TIMP2 were statistically significant. Conclusion The results of this study demonstrate that the gene expression of MMP9, MMP12, TIMP1 and TIMP2 was influenced by the addition of TGF-β1. These results may be translated to chronic venous insufficiency framework and suggest involvement of TGF-β1 in the vein wall pathology.

Keywords: Chronic venous insufficiency; matrix metalloproteinase; tissue inhibitor of metalloproteinase; transforming growth factor-beta1; vein wall.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Chronic Disease
  • Female
  • Gene Expression Regulation*
  • Humans
  • Male
  • Matrix Metalloproteinase 12 / biosynthesis*
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Middle Aged
  • Receptors, Transforming Growth Factor beta / biosynthesis*
  • Saphenous Vein / metabolism*
  • Saphenous Vein / pathology
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis*
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis*
  • Transforming Growth Factor beta1 / biosynthesis*
  • Venous Insufficiency / metabolism*
  • Venous Insufficiency / pathology

Substances

  • Receptors, Transforming Growth Factor beta
  • TGFB1 protein, human
  • TIMP1 protein, human
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta1
  • Tissue Inhibitor of Metalloproteinase-2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • MMP12 protein, human
  • Matrix Metalloproteinase 12