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The aim of this study was to investigate whether acute exposure to cigarette smoke extract altered VEGF production in lung parenchymal cells.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> We exposed human airway smooth muscle cells (ASMC), normal human lung fibroblasts (NHLF) and small airways epithelial cells (SAEC) to aqueous cigarette smoke extract (CSE) in order to investigate the effect of cigarette smoke on VEGF expression and release.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> Vascular endothelial growth factor release was elevated by sub\u2010toxic concentrations of CSE in both ASMC and NHLF, but not in SAEC. CSE\u2010evoked VEGF release was mimicked by its component acrolein at concentrations (10\u2013100\u2003\u00b5M) found in CSE, and prevented by the antioxidant and \u03b1,\u03b2\u2010unsaturated aldehyde scavenger, N\u2010acetylcysteine (NAC). Both CSE and acrolein (30\u2003\u00b5M) induced VEGF mRNA expression in ASMC cultures, suggesting an effect at transcriptional level. Crotonaldehyde and 4\u2010hydroxy\u20102\u2010nonenal, an endogenous \u03b1,\u03b2\u2010unsaturated aldehyde, stimulated VEGF release, as did H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. CSE\u2010evoked VEGF release was accompanied by rapid and lasting phosphorylation of p38 MAPK (mitogen\u2010activated protein kinase), which was abolished by NAC and mimicked by acrolein. Both CSE\u2010 and acrolein\u2010evoked VEGF release were blocked by selective inhibition of p38 MAPK signalling.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> \u03b1,\u03b2\u2010Unsaturated aldehydes and possibly reactive oxygen species contained in cigarette smoke stimulate VEGF expression and release from pulmonary cells through p38 MAPK signalling.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01253.x","type":"journal-article","created":{"date-parts":[[2011,2,10]],"date-time":"2011-02-10T12:30:21Z","timestamp":1297341021000},"page":"649-661","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Cigarette smoke and \u03b1,\u03b2\u2010unsaturated aldehydes elicit VEGF release through the p38 MAPK pathway in human airway smooth muscle cells and lung 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