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.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Koba
authors.initials: K
authors.lastname: Kupreishvili
authors.affiliation: Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands; Department of Cardiac Surgery, OLVG, Amsterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Stooker
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Reindert W
authors.initials: RW
authors.lastname: Emmens
authors.affiliation: Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands; Department of Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Alexander B A
authors.initials: ABA
authors.lastname: Vonk
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Sipkens
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: van Dijk
authors.affiliation: Department of Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Leon
authors.initials: L
authors.lastname: Eijsman
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Quax
authors.affiliation: Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands; Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Victor W M
authors.initials: VWM
authors.lastname: van Hinsbergh
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands. Electronic address: paj.krijnen@vumc.nl.
authors.forename: Paul A J
authors.initials: PAJ
authors.lastname: Krijnen
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands; Department of Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hans W M
authors.initials: HWM
authors.lastname: Niessen
mesh_terms: D017738:Alkanesulfonic Acids / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D062186:Arterial Pressure; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D009829:Oleic Acids / Q000494:pharmacology*; D064801:Phospholipase A2 Inhibitors / Q000494:pharmacology*; D012501:Saphenous Vein / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D013997:Time Factors
chemical_list: C545517:2-(N,N-bis(oleoyloxyethyl)amino)-1-ethanesulfonic acid; D017738:Alkanesulfonic Acids; D009829:Oleic Acids; D064801:Phospholipase A2 Inhibitors; D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human