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Procedure for Human Saphenous Veins Ex Vivo Perfusion and External Reinforcement
Published on: October 1, 2014
PX-18 Protects Human Saphenous Vein Endothelial Cells under Arterial Blood Pressure
Koba Kupreishvili1, Wim Stooker2, Reindert W Emmens1
1Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
Background:
Arterial blood pressure-induced shear stress causes endothelial cell apoptosis and inflammation in vein grafts after coronary artery bypass grafting. As the inflammatory protein type IIA secretory phospholipase A2 (sPLA2-IIA) has been shown to progress atherosclerosis, we hypothesized a role for sPLA2-IIA herein.
Methods:
The effects of PX-18, an inhibitor of both sPLA2-IIA and apoptosis, on residual endothelium and the presence of sPLA2-IIA were studied in human saphenous vein segments (n = 6) perfused at arterial blood pressure with autologous blood for 6 hrs.
Results:
The presence of PX-18 in the perfusion blood induced a significant 20% reduction in endothelial cell loss compared to veins perfused without PX18, coinciding with significantly reduced sPLA2-IIA levels in the media of the vein graft wall. In addition, PX-18 significantly attenuated caspase-3 activation in human umbilical vein endothelial cells subjected to shear stress via mechanical stretch independent of sPLA2-IIA.
Conclusions:
In conclusion, PX-18 protects saphenous vein endothelial cells from arterial blood pressure-induced death, possibly also independent of sPLA2-IIA inhibition.
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