Original Article
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World J Hypertens. Feb 23, 2014; 4(1): 7-14
Published online Feb 23, 2014. doi: 10.5494/wjh.v4.i1.7
ARB affects nicotine-induced gene expression profile in human coronary artery endothelial cells
Masataka Kudo, Ken Matsuda, Kaori Sugawara, Yuko Iki, Naotaka Kogure, Takako Saito-Ito, Kyoko Shimizu, Ikuko Sato, Takeo Yoshikawa, Akira Uruno, Ryo Ito, Atsushi Yokoyama, Akiko Saito-Hakoda, Sadayoshi Ito, Akira Sugawara
Masataka Kudo, Ken Matsuda, Sadayoshi Ito, Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
Kaori Sugawara, Yuko Iki, Naotaka Kogure, Takako Saito-Ito, Kyoko Shimizu, Ikuko Sato, Ryo Ito, Atsushi Yokoyama, Akiko Saito-Hakoda, Akira Sugawara, Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Takeo Yoshikawa, Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Akira Uruno, Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Author contributions: Kudo M prepared the manuscript; Kudo M, Matsuda K, Sugawara K, Iki Y, Kogure N, Saito-Ito T, Shimizu K, Sato I and Saito-Hakoda A performed the research; Yoshikawa T, Uruno A, Ito R and Yokoyama A advised on the research protocols; Ito S and Sugawara A supervised the research; Sugawara A revised the manuscript and gave the final approval.
Supported by Grants from Smoking Research Foundation (to Sugawara A)
Correspondence to: Akira Sugawara, MD, PhD, Professor, Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. akiras2i@med.tohoku.ac.jp
Telephone: +81-22-7177483 Fax: +81-22-7178083
Received: July 10, 2013
Revised: December 12, 2013
Accepted: January 15, 2014
Published online: February 23, 2014
Processing time: 229 Days and 23.2 Hours
Abstract

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.

Keywords: Angiotensin II; Atherosclerosis; Microarray; Olmesartan; Smoking

Core tip: Tobacco smoking is well known as one of the major risk factors for coronary heart disease and nicotine is recognized as the main addictive component. We investigate the effects of nicotine and nicotine plus angiotensin II receptor blocker (ARB) on the gene expression profile of human coronary artery endothelial cells. Nicotine induced changes in the gene expression profile related to “atherosclerosis signaling” may increase the risk for the initiation and progression of atherosclerosis. The inhibitory effect of ARB against the nicotine-induced gene expression profile may possibly induce anti-atherosclerotic effects against tobacco smoking independently of the lowering of the blood pressure.