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Variability of MMP/TIMP and TGF-β1 Receptors throughout the Clinical Progression of Chronic Venous Disease

Pedro Serralheiro1,2, António Novais3, Elisa Cairrão4

  • 1Norfolk and Norwich University Hospital, Norwich NR47UY, UK. pedro.serralheiro@nnuh.nhs.uk.

International Journal of Molecular Sciences
|December 22, 2017
PubMed

Insights

Chronic venous disease involves changes in matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). This study found decreased transforming growth factor-beta receptors (TGFβRs) expression in varicose veins, suggesting altered TGF-β1 involvement in disease progression.

Area of Science:

  • Vascular Biology
  • Molecular Medicine
  • Genetics

Background:

  • Chronic venous disease (CVeD) is a common condition with poorly understood pathophysiology.
  • Previous research on matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in varicose veins is inconsistent and ignores clinical progression.
  • Transforming growth factor-beta 1 (TGF-β1) and its receptors (TGFβRs) may influence MMP and TIMP expression in the vein wall.

Purpose of the Study:

  • To investigate genetic and immunohistochemical differences in healthy and CVeD great saphenous vein samples.
  • To analyze the expression of MMPs, TIMPs, and TGFβRs in relation to CVeD clinical progression and anatomical location.
  • To elucidate the role of TGF-β1 signaling in the MMP/TIMP imbalance in CVeD.

Main Methods:

  • Case-control study comparing healthy (n=13) and CVeD (early n=19, advanced n=12) great saphenous vein samples.
  • Quantitative polymerase chain reaction (qPCR) for gene expression analysis of MMPs, TIMPs, and TGFβRs.
  • Immunohistochemistry for protein localization of MMP2, TIMP2, and TGFβR2.

Main Results:

  • Varicose veins showed decreased gene expression of MMP12, TIMP2, TIMP3, TIMP4, and TGFβR2 compared to controls.
  • Advanced CVeD stages exhibited decreased MMP9 and TGFβR3 expression, and increased MMP2 and TIMP3 expression.
  • Immunohistochemistry results for the tunica intima generally aligned with qPCR findings.

Conclusions:

  • Reduced TGFβR expression in varicose veins suggests diminished TGF-β1 participation in the MMP/TIMP imbalance during CVeD progression.
  • Venous anatomical region and clinical stage are critical factors for understanding molecular events in the varicose vein wall.
  • Further research is needed to fully comprehend the molecular mechanisms underlying CVeD.
Keywords:
chronic venous diseasegene expressionmatrix metalloproteinases (MMPs)tissue inhibitors of metalloproteinases (TIMPs)transforming growth factor (TGF)-β receptorsvaricose vein

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