PMID- 19818091
OWN - NLM
STAT- MEDLINE
DCOM- 20110324
LR  - 20220317
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 14
IP  - 12
DP  - 2010 Dec
TI  - Effect of irreversibly glycated LDL in human vascular smooth muscle cells: lipid 
      loading, oxidative and inflammatory stress.
PG  - 2790-802
LID - 10.1111/j.1582-4934.2009.00933.x [doi]
AB  - The major complication of diabetes is accelerated atherosclerosis, the 
      progression of which entails complex interactions between the modified 
      low-density lipoproteins (LDL) and the cells of the arterial wall. Advanced 
      glycation end product-modified-LDL (AGE-LDL) that occurs at high rate in diabetes 
      contributes to diabetic atherosclerosis, but the underlying mechanisms are not 
      fully understood. The aim of this study was to assess the direct effect of 
      AGE-LDL on human vascular smooth muscle cells (hSMC) dysfunction. Cultured hSMC 
      incubated (24 hrs) with human AGE-LDL, native LDL (nLDL) or oxidized LDL (oxLDL) 
      were subjected to: (i) quantification of the expression of the receptors for 
      modified LDL and AGE proteins (LRP1, CD36, RAGE) and estimation of lipid loading, 
      (ii) determination of NADPH oxidase activity and reactive oxygen species (ROS) 
      production and (iii) evaluation of the expression of monocyte chemoattractant 
      protein-1 (MCP-1). The results show that exposure of hSMC to AGE-LDL (compared to 
      nLDL) induced: (a) increased NADPH oxidase activity (30%) and ROS production 
      (28%) by up-regulation of NOX1, NOX4, p22phox and p67phox expression, (b) 
      accumulation of intracellular cholesteryl esters, (c) enhanced gene expression of 
      LRP1 (160%) and CD36 (35%), and protein expression of LRP1, CD36 and RAGE, (d) 
      increased MCP-1 gene expression (160%) and protein secretion (300%) and (e) 
      augmented cell proliferation (30%). In conclusion, AGE-LDL activates hSMC 
      (increasing CD36, LRP1, RAGE), inducing a pro-oxidant state (activation of 
      NADPHox), lipid accumulation and a pro-inflammatory state (expression of MCP-1). 
      These results may partly explain the contribution of AGE-LDL and hSMC to the 
      accelerated atherosclerosis in diabetes.
CI  - (c) 2009 The Authors Journal compilation (c) 2010 Foundation for Cellular and 
      Molecular Medicine/Blackwell Publishing Ltd.
FAU - Sima, Anca V
AU  - Sima AV
AD  - Department of Lipoproteins and Atherosclerosis, Institute of Cellular Biology and 
      Pathology 'Nicolae Simionescu', Bucharest, Romania. anca.sima@icbp.ro
FAU - Botez, Gabriela M
AU  - Botez GM
FAU - Stancu, Camelia S
AU  - Stancu CS
FAU - Manea, Adrian
AU  - Manea A
FAU - Raicu, Monica
AU  - Raicu M
FAU - Simionescu, Maya
AU  - Simionescu M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Antigens, CD)
RN  - 0 (CD36 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (LRP1 protein, human)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-1)
RN  - 0 (Phosphoproteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (glycated lipoproteins, LDL)
RN  - 0 (neutrophil cytosol factor 67K)
RN  - EC 1.6.3.- (NADPH Oxidase 1)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.- (NOX1 protein, human)
RN  - EC 1.6.3.- (NOX4 protein, human)
RN  - EC 1.6.3.1 (CYBA protein, human)
SB  - IM
MH  - Antigens, CD/genetics
MH  - Arteries/cytology
MH  - Atherosclerosis/etiology
MH  - CD36 Antigens/genetics
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - Diabetes Complications
MH  - Endothelial Cells/chemistry/cytology/*metabolism
MH  - Gene Expression
MH  - Glycation End Products, Advanced/*metabolism
MH  - Humans
MH  - Inflammation
MH  - Lipoproteins, LDL/*metabolism
MH  - Low Density Lipoprotein Receptor-Related Protein-1/genetics
MH  - Muscle, Smooth, Vascular/cytology/*metabolism
MH  - NADPH Oxidase 1
MH  - NADPH Oxidase 4
MH  - NADPH Oxidases/genetics/metabolism
MH  - *Oxidative Stress
MH  - Phosphoproteins/genetics
MH  - Reactive Oxygen Species/blood
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/genetics/metabolism
PMC - PMC3822729
EDAT- 2009/10/13 06:00
MHDA- 2011/03/25 06:00
PMCR- 2010/12/01
CRDT- 2009/10/13 06:00
PHST- 2009/10/13 06:00 [entrez]
PHST- 2009/10/13 06:00 [pubmed]
PHST- 2011/03/25 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - JCMM933 [pii]
AID - 10.1111/j.1582-4934.2009.00933.x [doi]
PST - ppublish
SO  - J Cell Mol Med. 2010 Dec;14(12):2790-802. doi: 10.1111/j.1582-4934.2009.00933.x.