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Shear force regulates matrix metalloproteinase activity in human saphenous vein organ culture

M A Patterson1, C D Leville, C D Hower

  • 1Division of Vascular Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA.

The Journal of Surgical Research
|December 20, 2000
PubMed
Abstract

Insights

High blood flow increases matrix metalloproteinase (MMP) activity and intimal thickening in human saphenous vein grafts. This suggests shear force influences vein graft disease progression.

Area of Science:

  • Vascular Biology
  • Biomedical Engineering
  • Cardiovascular Research

Background:

  • Vein graft intimal hyperplasia is linked to shear stress and matrix metalloproteinases (MMPs).
  • Limited data exist on shear force's impact on MMP expression and activity.
  • This study investigates the relationship between shear force, MMP activity, and intimal thickening in human saphenous vein organ cultures.

Purpose of the Study:

  • To examine the relationship among shear force, metalloproteinase activity, and intimal thickening.
  • To investigate the influence of varying flow rates on human saphenous vein segments in organ culture.
  • To establish a model for analyzing physical forces' effects on intimal thickening.

Main Methods:

  • Human saphenous vein segments were cultured under static, low-flow, or high-flow conditions for 7 days.
  • Metalloproteinase levels and activities were quantified using ELISA and substrate gel zymography.
  • Intimal thickening was assessed morphometrically and compared to control tissue.

Main Results:

  • High flow increased proteolytic activity and MMP-2, MMP-9, TIMP-1, and TIMP-2 levels in vein tissue.
  • Intimal thickening was directly proportional to flow rate, increasing 3-fold in low-flow and 4-fold in high-flow conditions.
  • TIMP-2 increased with high flow in culture media, while TIMP-1 showed an inverse relationship with flow rate.

Conclusions:

  • Metalloproteinase levels in human saphenous vein cultures are significantly influenced by shear force.
  • MMP levels and activity demonstrate a strong correlation with the extent of intimal thickening.
  • This organ culture model offers a valuable platform for studying the impact of physical forces on vein graft intimal hyperplasia.

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