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

Koba Kupreishvili, Wim Stooker, Reindert W Emmens, Alexander B A Vonk, Jessica A Sipkens, Annemieke van Dijk, Leon Eijsman, Paul H Quax, Victor W M van Hinsbergh, Paul A J Krijnen, Hans W M Niessen

Research output: Contribution to journalArticleAcademicpeer-review

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 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.

Original languageEnglish
Pages (from-to)293-298
Number of pages6
JournalAnnals of Vascular Surgery
Volume42
DOIs
Publication statusPublished - Jul 2017

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