PX-18 Protects Human Saphenous Vein Endothelial Cells under Arterial Blood Pressure

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 A 2 (sPLA 2 -IIA) has been shown to progress atherosclerosis, we hypothesized a role for sPLA 2 -IIA herein. Methods The effects of PX-18, an inhibitor of both sPLA 2 -IIA and apoptosis, on residual endothelium and the presence of sPLA 2 -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 sPLA 2 -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 sPLA 2 -IIA. Conclusions In conclusion, PX-18 protects saphenous vein endothelial cells from arterial blood pressure–induced death, possibly also independent of sPLA 2 -IIA inhibition.