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

• Published in: Biochemical and biophysical research communications Vol. 344; no. 1; pp. 200 - 205
• Main Authors: Stielow, Claudia, Catar, Rusan A., Muller, Gregor, Wingler, Kirstin, Scheurer, Peter, Schmidt, Harald H.H.W., Morawietz, Henning
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26-05-2006
• Subjects: Benzoxazoles - chemistry; Benzoxazoles - pharmacology; Endothelial cells; 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; NAD(P)H oxidase; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - drug effects; NADPH Oxidases - metabolism; oxLDL; Reactive oxygen species; Reactive Oxygen Species - metabolism; RNA, Messenger - analysis; RNA, Messenger - metabolism; Superoxides - analysis; Triazoles - chemistry; Triazoles - pharmacology; VAS2870; oxLDL; Reactive oxygen species; VAS2870; NAD(P)H oxidase; Endothelial cells
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.03.114

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 50
μg/ml oxLDL for 2
h. 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.