Microarray analysis of nicotine-induced changes in gene expression in endothelial cells.
Cigarette smoking causes vascular endothelial dysfunction and is a major risk factor for cardiovascular diseases. Nicotine, a major constituent of cigarette smoke, has been shown to alter gene expression in endothelial cells; however, the regulatory pathways involved remain to be defined. We hypothesized that there might be distinct pathways that could be identified by systematic transcriptome analysis. Using the cDNA microarray approach, we ascertained the expression of over 4,000 genes in human coronary artery endothelial cells and identified a number of nicotine-modulated genes encoding a protein involving in signal transduction or transcriptional regulation. Among these were phosphatidylinositol phosphate kinase and diacylglycerol kinase, which are regulators of the inositol phospholipid pathway. Changes were also detected for transcription factors cAMP response element binding protein and nuclear factor-kappaB, of which the activities of both have been previously shown to be altered in nicotine-stimulated cells. The data from this study are relevant to understanding the mechanisms underlying the pathophysiological effect of nicotine and smoking, particularly on endothelial function and pathogenesis of atherosclerosis.
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Human Genetics Research Division, School of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
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D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000209:etiology / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D009206:Myocardium / Q000166:cytology*; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D009538:Nicotine / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010716:Phosphatidylinositols / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects
D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D009538:Nicotine