Arterial Blood Pressure Induces Transient C4b-Binding Protein in Human Saphenous Vein Grafts.
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.
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
Koba
K
Kupreishvili
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
Christof
C
Meischl
Department of Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Alexander B A
ABA
Vonk
Department of Cardiac Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
Wim
W
Stooker
Department of Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands; Department of Cardiac Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
Leon
L
Eijsman
Department of Translational Medicine, Lund University, Malmo, Sweden.
Anna M
AM
Blom
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Paul H A
PHA
Quax
Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.
Victor W M
VWM
van Hinsbergh
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Department of Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Hans W M
HWM
Niessen
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: paj.krijnen@vumc.nl.
Paul A J
PAJ
Krijnen
D000975:Antioxidants / Q000494:pharmacology; D062186:Arterial Pressure; D015933:Complement C3d / Q000378:metabolism; D050716:Complement C4b-Binding Protein / Q000378:metabolism*; D001026:Coronary Artery Bypass; D006801:Humans; D066298:In Vitro Techniques; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation*; D013997:Time Factors; D015854:Up-Regulation
D000975:Antioxidants; C055609:C4BPA protein, human; D050716:Complement C4b-Binding Protein; D015933:Complement C3d