Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation

被引：24

作者：

Fukuda, Kazuki ^{[1
]}

Matsumura, Takeshi ^{[1
]}

Senokuchi, Takafumi ^{[1
]}

Ishii, Norio ^{[1
]}

Kinoshita, Hiroyuki ^{[1
]}

Yamada, Sarie ^{[1
]}

Murakami, Saiko ^{[1
]}

Nakao, Saya ^{[2
]}

Motoshima, Hiroyuki ^{[1
]}

Kondo, Tatsuya ^{[1
]}

Kukidome, Daisuke ^{[1
]}

Kawasaki, Shuji ^{[1
]}

Kawada, Teruo ^{[3
]}

Nishikawa, Takeshi ^{[1
]}

Araki, Eiichi ^{[1
]}

机构：

[1] Kumamoto Univ, Fac Life Sci, Dept Metab Med, Kumamoto 8608556, Japan

[2] Prefectural Univ Kumamoto, Dept Environm & Symbiot Sci, Kumamoto, Japan

[3] Kyoto Univ, Grad Sch Agr, Div Food Sci & Biotechnol, Nutr Chem Lab, Kyoto, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 457卷 / 01期

基金：

日本学术振兴会;

关键词：

Statin; PPAR gamma; COX-2; Smooth muscle cell; Atherosclerosis; COA REDUCTASE INHIBITORS; PPAR-GAMMA; DEFICIENT MICE; ATHEROSCLEROSIS; EXPRESSION; MACROPHAGES; MIGRATION; ARTERY; MECHANISM; PATHWAY;

D O I：

10.1016/j.bbrc.2014.12.063

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The peroxisome proliferator-activated receptor-gamma (PPAR gamma) is an important regulator of lipid and glucose metabolism, and its activation is reported to suppress the progression of atherosclerosis. We have reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) activate PPAR gamma in macrophages. However, it is not yet known whether statins activate PPAR gamma in other vascular cells. In the present study, we investigated whether statins activate PPAR gamma in smooth muscle cells (SMCs) and endothelial cells (ECs) and thus mediate anti-atherosclerotic effects. Human aortic SMCs (HASMCs) and human umbilical vein ECs (HUVECs) were used in this study. Fluvastatin and pitavastatin activated PPAR gamma in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with COX-2-5iRNA abrogated statin-mediated PPAR gamma activation in HASMCs. Statins suppressed migration and proliferation of HASMCs, and inhibited lipopolysaccharide-induced expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (INF-alpha) in HASMCs. These effects of statins were abrogated by treatment with PPAR gamma-siRNA. Treatment with statins suppressed atherosclerotic lesion formation in Apoe(-/-) mice. In addition, transcriptional activity of PPAR gamma and CD36 expression were increased, and the expression of MCP-1 and TNF-alpha was decreased, in the aorta of statin-treated Apoe(-/-) mice. In conclusion, statins mediate anti-atherogenic effects through PPAR gamma activation in SMCs. These effects of statins on SMCs may be beneficial for the prevention of atherosclerosis. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：23 / 30

页数：8

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