Novel Nox inhibitor of oxLDL-induced reactive oxygen species formation in human endothelial cells.
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.
Stielow
Claudia
C
Department of Vascular Endothelium and Microcirculation, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Dresden, Germany.
Catar
Rusan A
RA
Muller
Gregor
G
Wingler
Kirstin
K
Scheurer
Peter
P
Schmidt
Harald H H W
HH
Morawietz
Henning
H
D001583:Benzoxazoles / Q000737:chemistry / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000032:analysis; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
C511179:3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo(4,5-d)pyrimidine; D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014230:Triazoles; C099252:oxidized low density lipoprotein; D013481:Superoxides; D019255:NADPH Oxidases