PMID- 21924076
OWN - NLM
STAT- MEDLINE
DCOM- 20120702
LR  - 20181201
IS  - 0253-3758 (Print)
IS  - 0253-3758 (Linking)
VI  - 39
IP  - 6
DP  - 2011 Jun
TI  - [Effect of atorvastatin on advanced glycation end products induced monocyte 
      chemoattractant protein-1 expression in cultured human endothelial cells].
PG  - 512-7
AB  - OBJECTIVE: To investigate the effects of atorvastatin on advanced glycation end 
      products (AGE) induced monocyte chemoattractant protein-1 (MCP-1) expression in 
      human umbilical vein endothelial cells (HUVECs) and whether this effect could be 
      linked to peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and nuclear 
      factor-kappaB (NF-kappaB). METHODS: Grouping: (1) Blank control group; (2) BSA group; (3) 
      AGE group: cells were incubated with different concentrations of AGE (10(-4), 
      10(-3), 10(-2) and 10(-1) g/L) for 24 hours; (4) AGE + Atorvastatin group: cells 
      were incubated with different concentrations of atorvastatin (0.1, 1, 10 micromol/L) 
      for 1 hour, then incubated with AGE (10(-1) g/L) for 24 hours; (5) PPAR-gamma agonist 
      (15 d-PGJ2) group: cells were incubated with 15 d-PGJ2 (10 micromol/L) for 1 hour, 
      then incubated with AGE (10(-1) g/L) for 24 hours; (6) PPAR-gamma inhibitor (GW9662) 
      group: cells were incubated with GW9662 (5000 nmol/L) for 1 hour, then incubated 
      with atorvastatin (1 micromol/L) and AGE (10(-1) g/L) for 24 hours. Collagenase was 
      used to isolate the endothelial cell from human umbilical vein; RT-PCR was 
      performed to examine the mRNA expression of MCP-1 and PPAR-gamma; Western blot was 
      performed to detect NF-kappaB p65 protein. RESULTS: (1) The expression of MCP-1 mRNA 
      was increased in proportion with increasing concentrations of AGEs which could be 
      blocked by atorvastatin in a dose-dependent manner. (2) AGE (10(-1) g/L) 
      significantly downregulated the expression of PPAR-gamma mRNA (0.22 +/- 0.08 vs. 0.69 +/- 
      0.09, P < 0.01) while upregulated the expression of phospho-NF-kappaB p65 protein 
      (0.78 +/- 0.06 vs. 0.31 +/- 0.01, P < 0.01) and nonphospho-NF-kappaB p65 protein (1.61 +/- 
      0.16 vs. 0.59 +/- 0.14, P < 0.01) compared with the control group which could be 
      significantly attenuated by atorvastatin. (3) PPAR-gamma agonist decreased the 
      expression of phospho-NF-kappaB p65 protein (0.21 +/- 0.01 vs. 0.78 +/- 0.06, P < 0.01), 
      nonphospho-NF-kappaB p65 protein (0.67 +/- 0.14 vs. 1.61 +/- 0.16, P < 0.01) and MCP-1 
      mRNA (0.17 +/- 0.02 vs. 0.93 +/- 0.12, P < 0.01) compared with AGE (10(-1) g/L) 
      group. (4) PPAR-gamma inhibitor antagonized the effect of atorvastatin on the 
      expression of phospho-NF-kappaB p65 protein, nonphospho-NF-kappaB p65 protein and MCP-1 
      mRNA stimulated by AGE in HUVECs (P < 0.01). CONCLUSION: The anti-inflammatory 
      properties of atorvastatin in AGE stimulated HUVECs may partly be attributed to 
      the effect on upregulation of PPAR-gamma and downregulation of NF-kappaB signaling 
      pathway.
FAU - Xu, Shang-Hua
AU  - Xu SH
AD  - Department of Cardiology, Affiliated Nanping First Hospital of Fujian Medical 
      University, Nanping 353000, China. xshanghua@medmail.com.cn
FAU - Wang, Ke-Feng
AU  - Wang KF
FAU - Xu, Chang-Sheng
AU  - Xu CS
FAU - Xie, Liang-di
AU  - Xie LD
LA  - chi
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Xin Xue Guan Bing Za Zhi
JT  - Zhonghua xin xue guan bing za zhi
JID - 7910682
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Heptanoic Acids)
RN  - 0 (PPAR gamma)
RN  - 0 (Pyrroles)
RN  - 0 (RELA protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor RelA)
RN  - A0JWA85V8F (Atorvastatin)
SB  - IM
MH  - Atorvastatin
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Glycation End Products, Advanced/*metabolism
MH  - Heptanoic Acids/*pharmacology
MH  - Human Umbilical Vein Endothelial Cells/drug effects/metabolism
MH  - Humans
MH  - PPAR gamma/metabolism
MH  - Pyrroles/*pharmacology
MH  - RNA, Messenger/genetics
MH  - Signal Transduction
MH  - Transcription Factor RelA/metabolism
EDAT- 2011/09/20 06:00
MHDA- 2012/07/03 06:00
CRDT- 2011/09/20 06:00
PHST- 2011/09/20 06:00 [entrez]
PHST- 2011/09/20 06:00 [pubmed]
PHST- 2012/07/03 06:00 [medline]
PST - ppublish
SO  - Zhonghua Xin Xue Guan Bing Za Zhi. 2011 Jun;39(6):512-7.