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 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.