PMID- 16600694
OWN - NLM
STAT- MEDLINE
DCOM- 20060829
LR  - 20171116
IS  - 1537-1891 (Print)
IS  - 1537-1891 (Linking)
VI  - 44
IP  - 6
DP  - 2006 Jun
TI  - Aspirin and PPAR-alpha activators inhibit monocyte chemoattractant protein-1 
      expression induced by high glucose concentration in human endothelial cells.
PG  - 440-9
AB  - Activated endothelial cells express monocyte chemoattractant protein-1 (MCP-1), a 
      chemokine which is reportedly involved in the recruitment of plasma monocytes in 
      the early stages of atherosclerosis. Since accelerated atherosclerosis is the 
      main complication of diabetes and both diseases encompass an inflammatory 
      reaction, we hypothesized that the anti-inflammatory drugs, aspirin and 
      peroxisome proliferator-activated receptor (PPAR-alpha) activators (fenofibrate 
      and clofibrate), could have an effect on the high glucose-induced MCP-1 
      expression in endothelial cells. To test this assumption, as well as the possible 
      mechanisms involved, the MCP-1 expression and secretion, the reactive oxygen 
      species levels, nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) 
      expression were determined in human endothelial cells exposed to high glucose 
      concentrations in the presence of aspirin, fenofibrate and clofibrate. Human 
      endothelial cells kept in normal glucose concentration in the absence of drugs 
      were used as control. The results showed that (i) aspirin, fenofibrate and 
      clofibrate decrease significantly the MCP-1 expression and secretion in human 
      endothelial cells; (ii) the high glucose up-regulated expression of MCP-1 in 
      endothelial cells was significantly reduced by inhibitors of NF-kB and reactive 
      oxygen species; (iii) all drugs notably decrease the level of the reactive oxygen 
      species and activation of NF-kB and AP-1. Together, the findings indicate that in 
      endothelial cells aspirin and PPAR-alpha activators reduce the high 
      glucose-increased expression of MCP-1 by a mechanism that includes the inhibition 
      of reactive oxygen species, and decrease of AP-1 and NF-kB activation.
FAU - Dragomir, Elena
AU  - Dragomir E
AD  - Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, 8, BP 
      Hasdeu Street, PO Box 35-14, 79691-Bucharest, Romania. elena.dragomir@icbp.ro
FAU - Tircol, Magdalena
AU  - Tircol M
FAU - Manduteanu, Ileana
AU  - Manduteanu I
FAU - Voinea, Manuela
AU  - Voinea M
FAU - Simionescu, Maya
AU  - Simionescu M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060405
PL  - United States
TA  - Vascul Pharmacol
JT  - Vascular pharmacology
JID - 101130615
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Onium Compounds)
RN  - 0 (PPAR alpha)
RN  - 0 (Peroxisome Proliferators)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factor RelA)
RN  - 402-71-1 (Tosylphenylalanyl Chloromethyl Ketone)
RN  - 6HJ411TU98 (diphenyleneiodonium)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - HPN91K7FU3 (Clofibrate)
RN  - IY9XDZ35W2 (Glucose)
RN  - R16CO5Y76E (Aspirin)
RN  - U202363UOS (Fenofibrate)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Aspirin/*pharmacology
MH  - Cell Line
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Clofibrate/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/*drug effects/enzymology
MH  - Fenofibrate/pharmacology
MH  - Gene Expression Regulation
MH  - Glucose/*pharmacology
MH  - Humans
MH  - NADPH Oxidases/metabolism
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Onium Compounds/pharmacology
MH  - PPAR alpha/*agonists/genetics/metabolism
MH  - Peroxisome Proliferators/*pharmacology
MH  - Proto-Oncogene Proteins c-jun/metabolism
MH  - Reactive Oxygen Species/antagonists & inhibitors/metabolism
MH  - Tosylphenylalanyl Chloromethyl Ketone/pharmacology
MH  - Transcription Factor RelA/metabolism
EDAT- 2006/04/08 09:00
MHDA- 2006/08/30 09:00
CRDT- 2006/04/08 09:00
PHST- 2005/10/19 00:00 [received]
PHST- 2006/02/16 00:00 [revised]
PHST- 2006/02/27 00:00 [accepted]
PHST- 2006/04/08 09:00 [pubmed]
PHST- 2006/08/30 09:00 [medline]
PHST- 2006/04/08 09:00 [entrez]
AID - S1537-1891(06)00054-1 [pii]
AID - 10.1016/j.vph.2006.02.006 [doi]
PST - ppublish
SO  - Vascul Pharmacol. 2006 Jun;44(6):440-9. doi: 10.1016/j.vph.2006.02.006. Epub 2006 
      Apr 5.