Loading...
Please wait, while we are loading the content...
Stable compounds of cigarette smoke induce endothelial superoxide anion production via NADPH oxidase activation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Jaimes, Edgar A. Demaster, Eugene G. Tian, Run-Xia Raij, Leopoldo |
| Copyright Year | 2004 |
| 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 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 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. |
| File Format | PDF HTM / HTML |
| DOI | 10.1161/01.ATV.0000127083.88549.58 |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/24/6/1031.full.pdf?download=true |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/early/2004/04/01/01.ATV.0000127083.88549.58.full.pdf |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/early/2004/04/01/01.ATV.0000127083.88549.58.full.pdf?download=true |
| PubMed reference number | 15059808 |
| Alternate Webpage(s) | https://doi.org/10.1161/01.ATV.0000127083.88549.58 |
| Journal | Medline |
| Volume Number | 24 |
| Issue Number | 6 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
