PMID- 25529449
OWN - NLM
STAT- MEDLINE
DCOM- 20150414
LR  - 20220310
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 457
IP  - 1
DP  - 2015 Jan 30
TI  - Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome 
      proliferator-activated receptor-gamma activation.
PG  - 23-30
LID - S0006-291X(14)02245-1 [pii]
LID - 10.1016/j.bbrc.2014.12.063 [doi]
AB  - The peroxisome proliferator-activated receptor-gamma (PPARgamma) 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 
      PPARgamma in macrophages. However, it is not yet known whether statins activate PPARgamma 
      in other vascular cells. In the present study, we investigated whether statins 
      activate PPARgamma 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 PPARgamma in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 
      (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with 
      COX-2-siRNA abrogated statin-mediated PPARgamma 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 (TNF-alpha) in HASMCs. These effects of statins 
      were abrogated by treatment with PPARgamma-siRNA. Treatment with statins suppressed 
      atherosclerotic lesion formation in Apoe(-/-) mice. In addition, transcriptional 
      activity of PPARgamma 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 PPARgamma activation in 
      SMCs. These effects of statins on SMCs may be beneficial for the prevention of 
      atherosclerosis.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Fukuda, Kazuki
AU  - Fukuda K
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Matsumura, Takeshi
AU  - Matsumura T
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan. Electronic address: takeshim@gpo.kumamoto-u.ac.jp.
FAU - Senokuchi, Takafumi
AU  - Senokuchi T
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Ishii, Norio
AU  - Ishii N
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Kinoshita, Hiroyuki
AU  - Kinoshita H
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Yamada, Sarie
AU  - Yamada S
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Murakami, Saiko
AU  - Murakami S
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Nakao, Saya
AU  - Nakao S
AD  - Department of Environmental & Symbiotic Sciences, Prefectural University of 
      Kumamoto, Kumamoto, Japan.
FAU - Motoshima, Hiroyuki
AU  - Motoshima H
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Kondo, Tatsuya
AU  - Kondo T
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Kukidome, Daisuke
AU  - Kukidome D
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Kawasaki, Shuji
AU  - Kawasaki S
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Kawada, Teruo
AU  - Kawada T
AD  - Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, 
      Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
FAU - Nishikawa, Takeshi
AU  - Nishikawa T
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Araki, Eiichi
AU  - Araki E
AD  - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 
      Kumamoto, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141219
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Apolipoproteins E)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR gamma)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 4L066368AS (Fluvastatin)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Animals
MH  - Aorta/pathology
MH  - Apolipoproteins E/deficiency/metabolism
MH  - Atherosclerosis/*drug therapy/enzymology/*metabolism/pathology
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Chemokine CCL2/metabolism
MH  - Cyclooxygenase 2/metabolism
MH  - Disease Progression
MH  - Fatty Acids, Monounsaturated/pharmacology
MH  - Fluvastatin
MH  - Human Umbilical Vein Endothelial Cells/drug effects/metabolism
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/*therapeutic use
MH  - Indoles/pharmacology
MH  - Lipopolysaccharides
MH  - Mice, Inbred C57BL
MH  - Myocytes, Smooth Muscle/drug effects/metabolism/pathology
MH  - NF-kappa B/metabolism
MH  - PPAR gamma/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Atherosclerosis
OT  - COX-2
OT  - PPARgamma
OT  - Smooth muscle cell
OT  - Statin
EDAT- 2014/12/23 06:00
MHDA- 2015/04/15 06:00
CRDT- 2014/12/23 06:00
PHST- 2014/12/10 00:00 [received]
PHST- 2014/12/12 00:00 [accepted]
PHST- 2014/12/23 06:00 [entrez]
PHST- 2014/12/23 06:00 [pubmed]
PHST- 2015/04/15 06:00 [medline]
AID - S0006-291X(14)02245-1 [pii]
AID - 10.1016/j.bbrc.2014.12.063 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2015 Jan 30;457(1):23-30. doi: 
      10.1016/j.bbrc.2014.12.063. Epub 2014 Dec 19.