1. PX-18 Protects Human Saphenous Vein Endothelial Cells under Arterial Blood Pressure.
- Author
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Kupreishvili K, Stooker W, Emmens RW, Vonk ABA, Sipkens JA, van Dijk A, Eijsman L, Quax PH, van Hinsbergh VWM, Krijnen PAJ, and Niessen HWM
- Subjects
- Apoptosis drug effects, Cells, Cultured, Endothelial Cells enzymology, Endothelial Cells pathology, Group II Phospholipases A2 metabolism, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells enzymology, Human Umbilical Vein Endothelial Cells pathology, Humans, Saphenous Vein enzymology, Saphenous Vein pathology, Time Factors, Alkanesulfonic Acids pharmacology, Arterial Pressure, Endothelial Cells drug effects, Group II Phospholipases A2 antagonists & inhibitors, Mechanotransduction, Cellular drug effects, Oleic Acids pharmacology, Phospholipase A2 Inhibitors pharmacology, Saphenous Vein drug effects
- Abstract
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 (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., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2017
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