PMID- 18586837
OWN - NLM
STAT- MEDLINE
DCOM- 20090130
LR  - 20211020
IS  - 1479-6813 (Electronic)
IS  - 0952-5041 (Print)
IS  - 0952-5041 (Linking)
VI  - 41
IP  - 3
DP  - 2008 Sep
TI  - Pigment epithelium-derived factor mitigates inflammation and oxidative stress in 
      retinal pericytes exposed to oxidized low-density lipoprotein.
PG  - 135-43
LID - 10.1677/JME-08-0011 [doi]
AB  - Oxidized and/or glycated low-density lipoprotein (LDL) may mediate capillary 
      injury in diabetic retinopathy. The mechanisms may involve pro-inflammatory and 
      pro-oxidant effects on retinal capillary pericytes. In this study, these effects, 
      and the protective effects of pigment epithelium-derived factor (PEDF), were 
      defined in a primary human pericyte model. Human retinal pericytes were exposed 
      to 100 microg/ml native LDL (N-LDL) or heavily oxidized glycated LDL (HOG-LDL) 
      with or without PEDF at 10-160 nM for 24 h. To assess pro-inflammatory effects, 
      monocyte chemoattractant protein-1 (MCP-1) secretion was measured by ELISA, and 
      nuclear factor-kappaB (NF-kappaB) activation was detected by immunocytochemistry. 
      Oxidative stress was determined by measuring intracellular reactive oxygen 
      species (ROS), peroxynitrite (ONOO(-)) formation, inducible nitric oxide synthase 
      (iNOS) expression, and nitric oxide (NO) production. The results showed that 
      MCP-1 was significantly increased by HOG-LDL, and the effect was attenuated by 
      PEDF in a dose-dependent manner. PEDF also attenuated the HOG-LDL-induced 
      NF-kappaB activation, suggesting that the inhibitory effect of PEDF on MCP-1 was 
      at least partially through the blockade of NF-kappaB activation. Further studies 
      demonstrated that HOG-LDL, but not N-LDL, significantly increased ONOO(-) 
      formation, NO production, and iNOS expression. These changes were also alleviated 
      by PEDF. Moreover, PEDF significantly ameliorated HOG-LDL-induced ROS generation 
      through up-regulation of superoxide dismutase 1 expression. Taken together, these 
      results demonstrate pro-inflammatory and pro-oxidant effects of HOG-LDL on 
      retinal pericytes, which were effectively ameliorated by PEDF. Suppressing MCP-1 
      production and thus inhibiting macrophage recruitment may represent a new 
      mechanism for the salutary effect of PEDF in diabetic retinopathy and warrants 
      more studies in future.
FAU - Zhang, Sarah X
AU  - Zhang SX
AD  - Department of Medicine Endocrinology, Harold Hamm Oklahoma Diabetes Center, 
      University of Oklahoma Health Sciences Center, 941 Stanton L. Young Boulevard, 
      331A, Oklahoma City, Oklahoma 73104, USA.
FAU - Wang, Joshua J
AU  - Wang JJ
FAU - Dashti, Azar
AU  - Dashti A
FAU - Wilson, Kenneth
AU  - Wilson K
FAU - Zou, Ming-Hui
AU  - Zou MH
FAU - Szweda, Luke
AU  - Szweda L
FAU - Ma, Jian-Xing
AU  - Ma JX
FAU - Lyons, Timothy J
AU  - Lyons TJ
LA  - eng
GR  - R01 HL074399-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL089920/HL/NHLBI NIH HHS/United States
GR  - R01 HL074399/HL/NHLBI NIH HHS/United States
GR  - R01 HL089920-01A1/HL/NHLBI NIH HHS/United States
GR  - P20RR024215/RR/NCRR NIH HHS/United States
GR  - R01 HL074399-04/HL/NHLBI NIH HHS/United States
GR  - P20 RR024215-02/RR/NCRR NIH HHS/United States
GR  - R01 HL079584/HL/NHLBI NIH HHS/United States
GR  - R01 EY012231/EY/NEI NIH HHS/United States
GR  - R01 HL096032/HL/NHLBI NIH HHS/United States
GR  - R01 HL079584-06/HL/NHLBI NIH HHS/United States
GR  - R01 HL079584-05/HL/NHLBI NIH HHS/United States
GR  - R01 HL080499-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL080499-02/HL/NHLBI NIH HHS/United States
GR  - R01 HL110488/HL/NHLBI NIH HHS/United States
GR  - R01 HL105157/HL/NHLBI NIH HHS/United States
GR  - P20 RR024215/RR/NCRR NIH HHS/United States
GR  - R01 HL080499/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080627
PL  - England
TA  - J Mol Endocrinol
JT  - Journal of molecular endocrinology
JID - 8902617
RN  - 0 (Chemokine CCL2)
RN  - 0 (Eye Proteins)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (NF-kappa B)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Serpins)
RN  - 0 (oxidized low density lipoprotein)
RN  - 0 (pigment epithelium-derived factor)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Eye Proteins/*pharmacology
MH  - Humans
MH  - Inflammation/*pathology
MH  - Lipoproteins, LDL/*pharmacology
MH  - NF-kappa B/metabolism
MH  - Nerve Growth Factors/*pharmacology
MH  - Nitric Oxide/biosynthesis
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Oxidative Stress/*drug effects
MH  - Pericytes/*drug effects/enzymology/*pathology
MH  - Peroxynitrous Acid/metabolism
MH  - Protein Transport/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Retina/*cytology/enzymology
MH  - Serpins/*pharmacology
MH  - Superoxide Dismutase/metabolism
MH  - Up-Regulation/drug effects
PMC - PMC2714421
MID - NIHMS113034
EDAT- 2008/07/01 09:00
MHDA- 2009/01/31 09:00
PMCR- 2009/09/01
CRDT- 2008/07/01 09:00
PHST- 2008/07/01 09:00 [pubmed]
PHST- 2009/01/31 09:00 [medline]
PHST- 2008/07/01 09:00 [entrez]
PHST- 2009/09/01 00:00 [pmc-release]
AID - JME-08-0011 [pii]
AID - 10.1677/JME-08-0011 [doi]
PST - ppublish
SO  - J Mol Endocrinol. 2008 Sep;41(3):135-43. doi: 10.1677/JME-08-0011. Epub 2008 Jun 
      27.