AIM: To investigate the effects of nicotine and nicotine plus angiotensin ‡U receptor blocker (ARB) on the gene expression profile of human coronary artery endothelial cells (HCAECs). METHODS: The changes in gene expression profiles in HCAECs treated with nicotine and nicotine plus ARB olmesartan were analyzed by DNA microarray. In nicotine- treated HCAECs, 432 genes selected by P < 0.01 were greater than 1.5-fold compared with the untreated cells. Data were analyzed using IPA (IngenuityR Systems, www.ingenuity.com). RESULTS: The gene expression levels of tumor necrosis factor-ƒ¿, collagen type 1, matrix metalloproteinase- 10, and disintegrin and metalloprotease domain 8, which are related to gcardiovascular function and diseaseh, were significantly increased. In canonical pathway analyses using IPA, gatherosclerosis signalingh was strongly affected by nicotine treatment and this effect was reduced by co-incubation with ARB olmesartan. These data indicate that the deleterious cardiovascular consequences of cigarette smoking may, at least in part, be due to the nicotine-induced gene expression profile related to gatherosclerosis signalingh. CONCLUSION: The inhibitory effect of ARB against the nicotine-induced gene expression profile may possibly induce anti-atherosclerotic effects that are independent of those from lowering the blood pressure.