title: Cigarette smoke is an endothelial stressor and leads to cell cycle arrest.
abstract: 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 on endothelial cells exposed to an aqueous cigarette smoke extract (CSE) for 3, 7, and 24 h, 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 was shown to be a 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 from CSE implying that reactive oxygen species are the main culprit. This was 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 a threefold increase in depolarised mitochondria after 6 h. Finally, cell cycle analysis showed the induction of G1 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.
authors.affiliation: Biocenter, Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, Innsbruck Medical University, Innsbruck, Austria. blair.henderson@i-med.ac.at
authors.forename: Blair
authors.initials: B
authors.lastname: Henderson
authors.forename: Adam
authors.initials: A
authors.lastname: Csordas
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Backovic
authors.forename: Michaela
authors.initials: M
authors.lastname: Kind
authors.forename: David
authors.initials: D
authors.lastname: Bernhard
authors.forename: Georg
authors.initials: G
authors.lastname: Wick
mesh_terms: D002453:Cell Cycle; D002469:Cell Separation; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008670:Metals; D008928:Mitochondria / Q000378:metabolism; D009538:Nicotine / Q000009:adverse effects*; D020411:Oligonucleotide Array Sequence Analysis; D017382:Reactive Oxygen Species; D012907:Smoking; D013997:Time Factors
chemical_list: D006360:Heat-Shock Proteins; D008670:Metals; D017382:Reactive Oxygen Species; D009538:Nicotine