Stable compounds of cigarette smoke induce endothelial superoxide anion production via NADPH oxidase activation.
Arterioscler Thromb Vasc Biol
; 24(6): 1031-6, 2004 Jun.
Article
em En
| MEDLINE
| ID: mdl-15059808
ABSTRACT
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 (O2*). In these studies, we investigated whether stable compounds present in CS activate specific pathways responsible for the increased endothelial O2* production. METHODS ANDRESULTS:
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 O2* 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 O2* 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 O2* 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fumaça
/
Nicotiana
/
Endotélio Vascular
/
Superóxidos
/
NADPH Oxidases
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos