PMID- 19850013
OWN - NLM
STAT- MEDLINE
DCOM- 20091229
LR  - 20171116
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 390
IP  - 3
DP  - 2009 Dec 18
TI  - Irreversibly glycated LDL induce oxidative and inflammatory state in human 
      endothelial cells; added effect of high glucose.
PG  - 877-82
LID - 10.1016/j.bbrc.2009.10.066 [doi]
AB  - In diabetes, hyperglycemia and the associated formation of advanced glycation 
      end-products (AGE) and AGE-modified low density lipoproteins (AGE-LDL) can 
      directly affect the cells of the vascular wall. We hypothesize that AGE-LDL may 
      act directly and induce oxidant and inflammatory alterations in human endothelial 
      cells (HEC), this effect being amplified by high glucose. To test this 
      assumption, the activity of NADPH oxidase (NADPHox) was evaluated and the 
      expression of its subunits (p22(phox), NOX4, and p67(phox)), of the AGE receptor 
      (RAGE), and of the monocyte chemoattractant protein-1 (MCP-1) were assessed by 
      real-time PCR and Western blot in confluent EA.hy926 cells incubated with AGE-LDL 
      for 24 and 48h, in normal and high glucose conditions. Exposure of HEC for 48h to 
      AGE-LDL in 5mM glucose induced an increase of RAGE expression (50%), NADPHox 
      activity (107%), p22(phox) and NOX4 mRNA (50% and 188%, respectively) and MCP-1 
      expression (80%). AGE-LDL-stimulated p22(phox) expression by activating p38 MAP 
      kinase and NF-kB, and MCP-1 expression by activating NF-kB, as demonstrated by 
      the use of specific inhibitors (SB203580 and Bay11-7085). The addition of 25mM 
      glucose in the culture medium enhanced the effect of AGE-LDL, but also of nLDL, 
      on RAGE, p22(phox), NOX4, p67(phox), and MCP-1 gene expression. In conclusion, 
      AGE-LDL induce an oxidative stress and a pro-inflammatory state in human 
      endothelial cells. Both AGE-LDL and nLDL in the presence of high glucose amplify 
      their effect, revealing a link between hyperlipidemia, diabetes, and endothelial 
      cell dysfunction.
FAU - Toma, Laura
AU  - Toma L
AD  - Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, 
      Romania.
FAU - Stancu, Camelia S
AU  - Stancu CS
FAU - Botez, Gabriela M
AU  - Botez GM
FAU - Sima, Anca V
AU  - Sima AV
FAU - Simionescu, Maya
AU  - Simionescu M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091020
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (BAY 11-7085)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Imidazoles)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Nitriles)
RN  - 0 (Pyridines)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Sulfones)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.- (NOX4 protein, human)
RN  - EC 1.6.3.1 (CYBA protein, human)
RN  - IY9XDZ35W2 (Glucose)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Cell Line
MH  - *Cell Proliferation
MH  - Chemokine CCL2/metabolism
MH  - Endothelium, Vascular/metabolism/*pathology
MH  - Gene Expression
MH  - Glucose/metabolism/pharmacology
MH  - Glycation End Products, Advanced/*metabolism/pharmacology
MH  - Humans
MH  - Hyperglycemia/*metabolism/*pathology
MH  - Imidazoles/pharmacology
MH  - Inflammation/metabolism/pathology
MH  - Lipoproteins, LDL/*metabolism/pharmacology
MH  - NADPH Oxidase 4
MH  - NADPH Oxidases/metabolism
MH  - Nitriles/pharmacology
MH  - Pyridines/pharmacology
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/metabolism
MH  - Sulfones/pharmacology
EDAT- 2009/10/24 06:00
MHDA- 2009/12/30 06:00
CRDT- 2009/10/24 06:00
PHST- 2009/10/12 00:00 [received]
PHST- 2009/10/13 00:00 [accepted]
PHST- 2009/10/24 06:00 [entrez]
PHST- 2009/10/24 06:00 [pubmed]
PHST- 2009/12/30 06:00 [medline]
AID - S0006-291X(09)02044-0 [pii]
AID - 10.1016/j.bbrc.2009.10.066 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2009 Dec 18;390(3):877-82. doi: 
      10.1016/j.bbrc.2009.10.066. Epub 2009 Oct 20.