Novel Nox inhibitor of oxLDL-induced reactive oxygen species formation in human endothelial cells

Claudia Stielow; Rusan A Catar; Gregor Muller; Kirstin Wingler; Peter Scheurer; Harald H H W Schmidt; Henning Morawietz

doi:10.1016/j.bbrc.2006.03.114

Novel Nox inhibitor of oxLDL-induced reactive oxygen species formation in human endothelial cells

Biochem Biophys Res Commun. 2006 May 26;344(1):200-5. doi: 10.1016/j.bbrc.2006.03.114. Epub 2006 Mar 29.

Authors

Claudia Stielow¹, Rusan A Catar, Gregor Muller, Kirstin Wingler, Peter Scheurer, Harald H H W Schmidt, Henning Morawietz

Affiliation

¹ Department of Vascular Endothelium and Microcirculation, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Dresden, Germany.

PMID: 16603125
DOI: 10.1016/j.bbrc.2006.03.114

Abstract

In this study, we investigated effects of a novel NAD(P)H oxidase (Nox)-inhibitor 3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine (VAS2870) on oxidized low-density lipoprotein (oxLDL)-mediated reactive oxygen species (ROS) formation in human endothelial cells. Primary cultures of human umbilical vein endothelial cells were cultured to confluence and ROS formation was induced with 50microg/ml oxLDL for 2h. ROS formation was detected by chemiluminescence (CL) using the Diogenes reagent. OxLDL induced ROS formation in human endothelial cells (171+/-12%; n=10, P<0.05 vs. control). This augmented ROS formation in response to oxLDL was completely inhibited by the Nox inhibitor VAS2870 (101+/-9%; n=7, P<0.05 vs. oxLDL). Similar results were obtained with superoxide dismutase (91+/-7%; n=7, P<0.05 vs. oxLDL). However, the Nox4 mRNA expression level was neither changed by oxLDL nor VAS2870. We conclude that VAS2870 could provide a novel strategy to inhibit the augmented endothelial superoxide anion formation in response to cardiovascular risk factors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzoxazoles / chemistry
Benzoxazoles / pharmacology*
Endothelial Cells / drug effects
Endothelial Cells / enzymology*
Endothelium, Vascular / cytology
Endothelium, Vascular / drug effects
Endothelium, Vascular / enzymology*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Lipoproteins, LDL / pharmacology
NADPH Oxidases / antagonists & inhibitors*
NADPH Oxidases / drug effects
NADPH Oxidases / metabolism
RNA, Messenger / analysis
RNA, Messenger / metabolism
Reactive Oxygen Species / metabolism*
Superoxides / analysis
Triazoles / chemistry
Triazoles / pharmacology*

Substances

3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo(4,5-d)pyrimidine
Benzoxazoles
Enzyme Inhibitors
Lipoproteins, LDL
RNA, Messenger
Reactive Oxygen Species
Triazoles
oxidized low density lipoprotein
Superoxides
NADPH Oxidases