P 52 PETN induced HO-1 expression in endothelial cells as a target for secondary prevention of endothelial dysfunction

Abstract

Introduction Pentaerytrithyltetranitrate (PETN) is a NO-donor which directly impacts protective effects on endothelial cells by enhancing hemeoxygenase-1 (HO-1) expression. This results in attenuation of growth factor induced endothelial cell activation. In a randomized controlled trial we could show that PETN, given to pregnant women during the second and third trimester, could delay preeclampsia to late pregnancy and achieve a profound risk reduction for IUGR. Objectives The aim of this to show the protective effect of PETN on endothelial cell function and integrity, in the presence of stress. Material and methods HUVEC were grown to confluence in the presence or absence of PETN and effect of thrombin induced stress was evaluated by Westernblot analysis of ERK activation and XCelligence analysis of endothelial monolayer resistance, as a parameter of disturbed monolayer permeability. Results ERK activation upon thrombin treatment was markedly reduced in the presence of PETN. Resistance collapse and increase of permeability due to thrombin treatment was clearly attenuated by PETN treatment. Conclusion These preliminary results would underscore the clinical results retrieved in our pilot trial and help to establish the concept of how PETN treatment could stabilize endothelial resistance to pregnancy induced stress. Improved endothelial function could well explain improved pregnancy outcome associated with improved fetoplacental perfusion.