Stable compounds of cigarette smoke induce endothelial superoxide anion production via NADPH oxidase activation

Edgar A. Jaimes, Eugene G. DeMaster, Run Xia Tian, Leopoldo Raij

Research output: Contribution to journalArticlepeer-review

194 Scopus citations

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 (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.

Original languageEnglish (US)
Pages (from-to)1031-1036
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number6
DOIs
StatePublished - Jun 2004

Keywords

  • Cigarette smoke
  • Endothelium
  • NADPH oxidase
  • Nitric oxide
  • Superoxide anion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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