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

Cite this

Kupreishvili, Koba ; Stooker, Wim ; Emmens, Reindert W ; Vonk, Alexander B A ; Sipkens, Jessica A ; van Dijk, Annemieke ; Eijsman, Leon ; Quax, Paul H ; van Hinsbergh, Victor W M ; Krijnen, Paul A J ; Niessen, Hans W M. / PX-18 Protects Human Saphenous Vein Endothelial Cells under Arterial Blood Pressure. In: Annals of Vascular Surgery. 2017 ; Vol. 42. pp. 293-298.
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title = "PX-18 Protects Human Saphenous Vein Endothelial Cells under Arterial Blood Pressure",
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.",
keywords = "Journal Article",
author = "Koba Kupreishvili and Wim Stooker and Emmens, {Reindert W} and Vonk, {Alexander B A} and Sipkens, {Jessica A} and {van Dijk}, Annemieke and Leon Eijsman and Quax, {Paul H} and {van Hinsbergh}, {Victor W M} and Krijnen, {Paul A J} and Niessen, {Hans W M}",
note = "Copyright {\circledC} 2017 Elsevier Inc. All rights reserved.",
year = "2017",
month = "7",
doi = "10.1016/j.avsg.2016.10.063",
language = "English",
volume = "42",
pages = "293--298",
journal = "Annals of Vascular Surgery",
issn = "0890-5096",
publisher = "Elsevier Inc.",

}

Kupreishvili, K, Stooker, W, Emmens, RW, Vonk, ABA, Sipkens, JA, van Dijk, A, Eijsman, L, Quax, PH, van Hinsbergh, VWM, Krijnen, PAJ & Niessen, HWM 2017, 'PX-18 Protects Human Saphenous Vein Endothelial Cells under Arterial Blood Pressure' Annals of Vascular Surgery, vol. 42, pp. 293-298. https://doi.org/10.1016/j.avsg.2016.10.063

PX-18 Protects Human Saphenous Vein Endothelial Cells under Arterial Blood Pressure. / Kupreishvili, Koba; Stooker, Wim; Emmens, Reindert W; Vonk, Alexander B A; Sipkens, Jessica A; van Dijk, Annemieke; Eijsman, Leon; Quax, Paul H; van Hinsbergh, Victor W M; Krijnen, Paul A J; Niessen, Hans W M.

In: Annals of Vascular Surgery, Vol. 42, 07.2017, p. 293-298.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - PX-18 Protects Human Saphenous Vein Endothelial Cells under Arterial Blood Pressure

AU - Kupreishvili, Koba

AU - Stooker, Wim

AU - Emmens, Reindert W

AU - Vonk, Alexander B A

AU - Sipkens, Jessica A

AU - van Dijk, Annemieke

AU - Eijsman, Leon

AU - Quax, Paul H

AU - van Hinsbergh, Victor W M

AU - Krijnen, Paul A J

AU - Niessen, Hans W M

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2017/7

Y1 - 2017/7

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.avsg.2016.10.063

DO - 10.1016/j.avsg.2016.10.063

M3 - Article

VL - 42

SP - 293

EP - 298

JO - Annals of Vascular Surgery

JF - Annals of Vascular Surgery

SN - 0890-5096

ER -