PMID- 21651980
OWN - NLM
STAT- MEDLINE
DCOM- 20110915
LR  - 20211020
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1812
IP  - 9
DP  - 2011 Sep
TI  - Atorvastatin exerts its anti-atherosclerotic effects by targeting the receptor 
      for advanced glycation end products.
PG  - 1130-7
LID - 10.1016/j.bbadis.2011.05.007 [doi]
AB  - Recent studies demonstrated the beneficial role of atorvastatin in reducing the 
      risk of cardiovascular morbidity and mortality in patients with diabetes mellitus 
      and/or metabolic syndrome. To investigate the mechanisms underlying the 
      anti-atheroscleroic action of atorvastatin, we examined the expression of the 
      receptor for advanced glycation end products (RAGE) and its downstream target 
      gene, monocyte chemoattractant protein-1 (MCP-1) using real-time PCR. In in vitro 
      studies, exposure to high glucose or AGE induced oxidative stress and activation 
      of the AGE/RAGE system in human umbilical vein endothelial cells. Treatment of 
      the cells with atorvastatin significantly released the oxidative stress by 
      restoring the levels of glutathione and inhibited the RAGE upregulation. In 
      diabetic Goto Kakisaki (GK) rats fed with a high-fat diet for 12weeks, RAGE and 
      MCP-1 were upregulated in the aortas, and there was a significant correlation 
      between RAGE and MCP-1 mRNA abundance (r=0.482, P=0.031). Treatment with 
      atorvastatin (20mg/kg qd) significantly downregulated the expression of RAGE and 
      MCP-1. These data thus demonstrate a novel "pleiotropic" activity of atorvastatin 
      in reducing the risk of cardiovascular diseases by targeting RAGE expression.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Feng, Bo
AU  - Feng B
AD  - Department of Endocrinology, The Affiliated East Hospital, Tongji University, 
      Shanghai, PR China. fengbo@medmail.com.cn
FAU - Xu, Lei
AU  - Xu L
FAU - Wang, Hua
AU  - Wang H
FAU - Yan, Xinfeng
AU  - Yan X
FAU - Xue, Junli
AU  - Xue J
FAU - Liu, Fengjing
AU  - Liu F
FAU - Hu, Ji-Fan
AU  - Hu JF
LA  - eng
GR  - R43 CA103553/CA/NCI NIH HHS/United States
GR  - R43 CA103553-01/CA/NCI NIH HHS/United States
GR  - 1R46CA103553-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110530
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Heptanoic Acids)
RN  - 0 (Pyrroles)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - A0JWA85V8F (Atorvastatin)
SB  - IM
MH  - Animals
MH  - Atorvastatin
MH  - Heptanoic Acids/*pharmacology
MH  - Humans
MH  - Microscopy, Electron, Transmission
MH  - Oxidative Stress
MH  - Pyrroles/*pharmacology
MH  - Rats
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic
PMC - PMC3143240
MID - NIHMS301479
EDAT- 2011/06/10 06:00
MHDA- 2011/09/16 06:00
PMCR- 2012/09/01
CRDT- 2011/06/10 06:00
PHST- 2011/01/27 00:00 [received]
PHST- 2011/05/12 00:00 [revised]
PHST- 2011/05/19 00:00 [accepted]
PHST- 2011/06/10 06:00 [entrez]
PHST- 2011/06/10 06:00 [pubmed]
PHST- 2011/09/16 06:00 [medline]
PHST- 2012/09/01 00:00 [pmc-release]
AID - S0925-4439(11)00120-7 [pii]
AID - 10.1016/j.bbadis.2011.05.007 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2011 Sep;1812(9):1130-7. doi: 10.1016/j.bbadis.2011.05.007. 
      Epub 2011 May 30.