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Published on: October 1, 2014
Arterial Blood Pressure Induces Transient C4b-Binding Protein in Human Saphenous Vein Grafts
Koba Kupreishvili1, Christof Meischl1, Alexander B A Vonk2
1Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
Insights
Arterial blood pressure causes transient C4b-binding protein (C4bp) presence in vein walls, potentially protecting against graft failure. This finding highlights C4bp
Area of Science:
- Vascular Biology
- Complement System
- Immunology
Background:
- Complement activation contributes to vein graft failure under arterial pressure.
- Human saphenous veins exhibit cell-protective mechanisms.
- Investigated the presence of C4b-binding protein (C4bp) in vein walls.
Purpose of the Study:
- To determine if C4b-binding protein (C4bp), an endogenous complement inhibitor, is present in the vein wall.
- To understand the role of C4bp in response to arterial pressure in vein grafts.
Main Methods:
- Human saphenous vein segments (n=55) were perfused in vitro with autologous blood at arterial pressure for 1-6 hours.
- Segments were analyzed for C4bp and C3d deposition using immunohistochemistry.
- Experiments included perfusion with N-acetylcysteine to assess reactive oxygen species scavenging.
Main Results:
- Perfusion led to significant, time-dependent deposition of C3d and C4bp in the vein media, peaking at 4 hours.
- After 6 hours, C3d and C4bp levels decreased significantly, indicating transient presence.
- N-acetylcysteine treatment increased areas positive for both C4bp and C3d.
Conclusions:
- Arterial blood pressure exposure induces a transient presence of C4bp in the vein wall.
- This transient C4bp may act as a cell-protective mechanism against arterial pressure-induced stress and inflammation.
- Findings suggest a role for C4bp in mitigating vein graft failure.
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.
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