Cigarette smoke is an endothelial stressor and leads to cell cycle arrest

The molecular mechanisms underlying the atherogenic activity of cigarette smoke have yet to be fully elucidated. In the present study, genome-wide microarray analysis was performed oil endothelial cells exposed to an aqueous cigarette stroke extract (CSE) for 3, 7, and 24h, to obtain a better insight into how smoking may lead to endothelial damage. Microarray analysis showed the transcriptional response to CSE Was dominated by heat shock. stress responsive. and inflammatory genes, along with genes encoding for anti-oxidant and metal detoxification proteins. The heat shock response wits shown to be it result of short lived reactive species of CSE. with the abrogation of the effect by the addition of old CSE, the anti-oxidant N-acetyl cysteine, or the removal of metals front CSE implying that reactive oxygen species are the main culprit. This wits further Supported by a strong decline in the level of intracellular protein oxidation levels seen Under these conditions compared to freshly prepared CSE. Mitochondrial integrity was also found to be significantly compromised after CSE treatment. resulting in it threefold increase in depolarised mitochondria after 6 h. Finally, cell cycle analysis showed the induction of GI cell cycle arrest. An increased stress and inflammation response indicates that endothelial damage from smoking could contribute to immune cell infiltration, while decreased growth rates reduce endothelial layer repair, promoting atherogenesis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.