TY - JOUR
T1 - Stable compounds of cigarette smoke induce endothelial superoxide anion production via NADPH oxidase activation
AU - Jaimes, Edgar A.
AU - DeMaster, Eugene G.
AU - Tian, Run Xia
AU - Raij, Leopoldo
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2004/6
Y1 - 2004/6
N2 - Objective-Endothelial dysfunction is an early manifestation of cigarette smoke (CS) toxicity. We have previously demonstrated that CS impairs nitric oxide (NO)-mediated endothelial function via increased generation of superoxide anion (O 2 .-). In these studies, we investigated whether stable compounds present in CS activate specific pathways responsible for the increased endothelial O 2 .- production. Methods and Results-Short exposure of bovine pulmonary artery endothelial cells (BPAECs), human pulmonary artery endothelial cells, and rat pulmonary arteries to CS extracts (CSEs) resulted in a large increase in O 2 .- production (20-fold, 3-fold, and 2-fold increase, respectively; P<0.05 versus control), which was inhibited by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodinium, apocynin, and gp91 docking sequence-tat peptide but not by oxypurinol, the NO synthase inhibitor N G-nitro-L-arginine methyl ester, or the mitochondrial respiration inhibitor rotenone. Exposure of BPAECs to acrolein, a stable thiol-reactive agent found in CS, increased O 2 .- production 5-fold, which was prevented by prior inhibition of NADPH oxidase. Conclusions-These studies demonstrate that thiol-reactive stable compounds in CS can activate NADPH oxidase and increase endothelial O 2 .- production, thereby reducing NO bioactivity and resulting in endothelial dysfunction. Clinically, these studies may contribute to the development of agents able to mitigate CS-mediated vascular toxicity.
AB - Objective-Endothelial dysfunction is an early manifestation of cigarette smoke (CS) toxicity. We have previously demonstrated that CS impairs nitric oxide (NO)-mediated endothelial function via increased generation of superoxide anion (O 2 .-). In these studies, we investigated whether stable compounds present in CS activate specific pathways responsible for the increased endothelial O 2 .- production. Methods and Results-Short exposure of bovine pulmonary artery endothelial cells (BPAECs), human pulmonary artery endothelial cells, and rat pulmonary arteries to CS extracts (CSEs) resulted in a large increase in O 2 .- production (20-fold, 3-fold, and 2-fold increase, respectively; P<0.05 versus control), which was inhibited by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodinium, apocynin, and gp91 docking sequence-tat peptide but not by oxypurinol, the NO synthase inhibitor N G-nitro-L-arginine methyl ester, or the mitochondrial respiration inhibitor rotenone. Exposure of BPAECs to acrolein, a stable thiol-reactive agent found in CS, increased O 2 .- production 5-fold, which was prevented by prior inhibition of NADPH oxidase. Conclusions-These studies demonstrate that thiol-reactive stable compounds in CS can activate NADPH oxidase and increase endothelial O 2 .- production, thereby reducing NO bioactivity and resulting in endothelial dysfunction. Clinically, these studies may contribute to the development of agents able to mitigate CS-mediated vascular toxicity.
KW - Cigarette smoke
KW - Endothelium
KW - NADPH oxidase
KW - Nitric oxide
KW - Superoxide anion
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U2 - 10.1161/01.ATV.0000127083.88549.58
DO - 10.1161/01.ATV.0000127083.88549.58
M3 - Article
C2 - 15059808
AN - SCOPUS:2942541144
VL - 24
SP - 1031
EP - 1036
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 6
ER -