Microarray analysis of nicotine-induced changes in gene expression in endothelial cells

Cigarette smoking causes vascular endothelial dysfunction and is a major ri sk factor for cardiovascular diseases. Nicotine, a major constituent of cig arette smoke, has been shown to alter gene expression in endothelial cells; however, the regulatory pathways involved remain to be defined. We hypothe sized that there might be distinct pathways that could be identified by sys tematic transcriptome analysis. Using the cDNA microarray approach, we asce rtained the expression of over 4,000 genes in human coronary artery endothe lial cells and identified a number of nicotine-modulated genes encoding a p rotein involving in signal transduction or transcriptional regulation. Amon g these were phosphatidylinositol phosphate kinase and diacylglycerol kinas e, which are regulators of the inositol phospholipid pathway. Changes were also detected for transcription factors cAMP response element binding prote in and nuclear factor-kappaB, of which the activities of both have been pre viously shown to be altered in nicotine-stimulated cells. The data from thi s study are relevant to understanding the mechanisms underlying the pathoph ysiological effect of nicotine and smoking, particularly on endothelial fun ction and pathogenesis of atherosclerosis.