AIM: To investigate the effects of nicotine and nicotine plus angiotensin Ⅱ receptor blocker(ARB) on the gene expression profile of human coronary artery endothelial cells(HCAECs).METHODS: The changes in gene express...AIM: To investigate the effects of nicotine and nicotine plus angiotensin Ⅱ 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(Ingenuity? Systems, www.ingenuity.com).RESULTS: The gene expression levels of tumor necrosis factor-α, collagen type 1, matrix metalloproteinase-10, and disintegrin and metalloprotease domain 8, which are related to "cardiovascular function and disease", were significantly increased. In canonical pathway analyses using IPA, "atherosclerosis signaling" 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 "atherosclerosis signaling".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.展开更多
基金Supported by Grants from Smoking Research Foundation(to Sugawara A)
文摘AIM: To investigate the effects of nicotine and nicotine plus angiotensin Ⅱ 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(Ingenuity? Systems, www.ingenuity.com).RESULTS: The gene expression levels of tumor necrosis factor-α, collagen type 1, matrix metalloproteinase-10, and disintegrin and metalloprotease domain 8, which are related to "cardiovascular function and disease", were significantly increased. In canonical pathway analyses using IPA, "atherosclerosis signaling" 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 "atherosclerosis signaling".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.
