PMID- 17464346
OWN - NLM
STAT- MEDLINE
DCOM- 20070917
LR  - 20161124
IS  - 0829-8211 (Print)
IS  - 0829-8211 (Linking)
VI  - 85
IP  - 1
DP  - 2007 Feb
TI  - The inhibitory effect of simvastatin on the ADMA-induced inflammatory reaction is 
      mediated by MAPK pathways in endothelial cells.
PG  - 66-77
AB  - Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide 
      synthase, is emerging as a key contributor for endothelial dysfunction associated 
      with inflammation. Statins can inhibit vascular inflammatory reaction and improve 
      endothelial function. The aim of this study was to investigate in human 
      endothelial cells the signaling pathways of ADMA-induced inflammatory reaction 
      and potential inhibitory effects of simvastatin. Endothelial cells were cultured 
      and used for all of the studies. Tumor necrosis factor-alpha(TNF-alpha) and 
      soluble intercellular adhesion molecule-1 (sICAM-1) were determined by 
      enzyme-linked immunosorbent assay. Nuclear factor-kappaB (NF-kappaB) was assayed 
      by electrophoretic mobility shift assay. The activation of mitogen-activated 
      protein kinases (MAPKs), including p38 MAPK and extracellular signal-related 
      kinase (ERK(1/2)), were characterized by Western blot analysis. Treatment with 
      ADMA (3-30 micromol/L) increased the concentration of sICAM-1 in a dose-dependent 
      manner. ADMA (30 micromol/L) significantly enhanced the concentrations of 
      TNF-alpha and sICAM-1, the activity of NF-kappaB and the phosphorylation of p38 
      MAPK and ERK(1/2). The increased secretion of TNF-alpha and sICAM-1 and the 
      increased activity of NF-kappaB by ADMA were altered by SB203580 (5 micromol/L) 
      or PD98059 (20 micromol/L), but not by LY294002 (20 micromol/L). Simvastatin 
      (0.1, 0.5, or 2.5 micromol/L) markedly inhibited the elevated concentrations of 
      TNF-alpha and sICAM-1, the activity of NF-kappaB, and the phosphorylation of p38 
      MAPK and ERK(1/2) induced by ADMA. Simvastatin inhibited ADMA-induced 
      inflammatory reaction by p38 MAPK and ERK(1/2) pathways in cultured endothelial 
      cells.
FAU - Jiang, Jun-Lin
AU  - Jiang JL
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Central South 
      University, Xiang-Ya Road #110, Changsha 410078, China.
FAU - Wang, Shan
AU  - Wang S
FAU - Li, Nian-Sheng
AU  - Li NS
FAU - Zhang, Xiao-Hong
AU  - Zhang XH
FAU - Deng, Han-Wu
AU  - Deng HW
FAU - Li, Yuan-Jian
AU  - Li YJ
LA  - eng
PT  - Journal Article
PL  - Canada
TA  - Biochem Cell Biol
JT  - Biochemistry and cell biology = Biochimie et biologie cellulaire
JID - 8606068
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 63CV1GEK3Y (N,N-dimethylarginine)
RN  - 94ZLA3W45F (Arginine)
RN  - AGG2FN16EV (Simvastatin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Arginine/*analogs & derivatives/pharmacology
MH  - Cells, Cultured
MH  - Endothelial Cells/drug effects/*metabolism
MH  - Endothelium, Vascular/cytology
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - MAP Kinase Signaling System/drug effects/*physiology
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide Synthase/antagonists & inhibitors/metabolism
MH  - Phosphorylation
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Signal Transduction/*physiology
MH  - Simvastatin/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2007/04/28 09:00
MHDA- 2007/09/18 09:00
CRDT- 2007/04/28 09:00
PHST- 2007/04/28 09:00 [pubmed]
PHST- 2007/09/18 09:00 [medline]
PHST- 2007/04/28 09:00 [entrez]
AID - o06-146 [pii]
AID - 10.1139/o06-146 [doi]
PST - ppublish
SO  - Biochem Cell Biol. 2007 Feb;85(1):66-77. doi: 10.1139/o06-146.