Arterial Blood Pressure Induces Transient C4b-Binding Protein in Human Saphenous Vein Grafts

Ann Vasc Surg. 2017 May;41:259-264. doi: 10.1016/j.avsg.2016.10.033. Epub 2017 Feb 3.

Abstract

Background: Complement is an important mediator in arterial blood pressure-induced vein graft failure. Previously, we noted activation of cell protective mechanisms in human saphenous veins too. Here we have analyzed whether C4b-binding protein (C4bp), an endogenous complement inhibitor, is present in the vein wall.

Methods: Human saphenous vein segments obtained from patients undergoing coronary artery bypass grafting (n = 55) were perfused in vitro at arterial blood pressure with either autologous blood for 1, 2, 4, or 6 hr or with autologous blood supplemented with reactive oxygen species scavenger N-acetylcysteine. The segments were subsequently analyzed quantitatively for presence of C4bp and complement activation product C3d using immunohistochemistry.

Results: Perfusion induced deposition of C3d and C4bp within the media of the vessel wall, which increased reproducibly and significantly over a period of 4 hr up to 3.8% for C3d and 81% for C4bp of the total vessel area. Remarkably after 6 hr of perfusion, the C3d-positive area decreased significantly to 1.3% and the C4bp-positive area to 19% of the total area of the vein. The areas positive for both C4bp and C3d were increased in the presence of N-acetylcysteine.

Conclusions: Exposure to arterial blood pressure leads to a transient presence of C4bp in the vein wall. This may be part of a cell-protective mechanism to counteract arterial blood pressure-induced cellular stress and inflammation in grafted veins.

MeSH terms

  • Antioxidants / pharmacology
  • Arterial Pressure*
  • Complement C3d / metabolism
  • Complement C4b-Binding Protein / metabolism*
  • Coronary Artery Bypass*
  • Humans
  • In Vitro Techniques
  • Saphenous Vein / drug effects
  • Saphenous Vein / metabolism*
  • Saphenous Vein / transplantation*
  • Time Factors
  • Up-Regulation

Substances

  • Antioxidants
  • C4BPA protein, human
  • Complement C4b-Binding Protein
  • Complement C3d