The use of external mesh reinforcement to reduce intimal hyperplasia and preserve the structure of human saphenous veins

Biomaterials. 2014 Mar;35(9):2588-99. doi: 10.1016/j.biomaterials.2013.12.041. Epub 2014 Jan 13.

Abstract

The saphenous vein is the conduit of choice in bypass graft procedures. Haemodynamic factors play a major role in the development of intimal hyperplasia (IH), and subsequent bypass failure. To evaluate the potential protective effect of external reinforcement on such a failure, we developed an ex vivo model for the perfusion of segments of human saphenous veins under arterial shear stress. In veins submitted to pulsatile high pressure (mean pressure at 100 mmHg) for 3 or 7 days, the use of an external macroporous polyester mesh 1) prevented the dilatation of the vessel, 2) decreased the development of IH, 3) reduced the apoptosis of smooth muscle cells, and the subsequent fibrosis of the media layer, 4) prevented the remodelling of extracellular matrix through the up-regulation of matrix metalloproteinases (MMP-2, MMP-9) and plasminogen activator type I. The data show that, in an experimental ex vivo setting, an external scaffold decreases IH and maintains the integrity of veins exposed to arterial pressure, via increase in shear stress and decrease wall tension, that likely contribute to trigger selective molecular and cellular changes.

Keywords: Caspase-3; External polyester mesh reinforcement; Intimal hyperplasia; MMPs; Shear stress; Vein graft.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Caspase 3 / metabolism
  • Down-Regulation
  • Ephrin-B2 / genetics
  • Ephrin-B2 / metabolism
  • Female
  • Heme Oxygenase (Decyclizing) / metabolism
  • Humans
  • Hyperplasia
  • In Vitro Techniques
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Nitric Oxide Synthase Type III / metabolism
  • Perfusion
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Pressure
  • Receptor, EphB4 / genetics
  • Receptor, EphB4 / metabolism
  • Saphenous Vein / enzymology
  • Saphenous Vein / pathology*
  • Stress, Mechanical
  • Tissue Scaffolds / chemistry*
  • Transforming Growth Factor beta / metabolism
  • Tunica Intima / pathology*

Substances

  • Ephrin-B2
  • Plasminogen Activator Inhibitor 1
  • Transforming Growth Factor beta
  • Nitric Oxide Synthase Type III
  • Heme Oxygenase (Decyclizing)
  • Receptor, EphB4
  • Caspase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9