PMID- 17045925
OWN - NLM
STAT- MEDLINE
DCOM- 20070202
LR  - 20131121
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 41
IP  - 10
DP  - 2006 Nov 15
TI  - Role of redox factor-1 in hyperhomocysteinemia-accelerated atherosclerosis.
PG  - 1566-77
AB  - Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. We 
      have previously shown that homocysteine can induce monocyte chemoattractant 
      protein-1 (MCP-1) secretion via reactive oxygen species (ROS) in human monocytes 
      in vitro. In the present study, we investigated whether redox factor-1 (Ref-1) is 
      involved in HHcy-accelerated atherosclerosis. We used a mild HHcy animal model, 
      aortic roots and peritoneal macrophages were isolated for immunohistochemistry 
      and Western blotting, from apoE-/- and C57BL/6J mice fed a high Hcy diet (1.8 
      g/L) for 4 or 12 weeks. Four-week HHcy apoE-/- mice showed more plaques and 
      significantly increased immunostaining of Ref-1 and MCP-1 in foam cells, and HHcy 
      mice showed enhanced Ref-1 expression in peritoneal macrophages. To explore the 
      mediating mechanism, incubation with Hcy (100 microM) increased Ref-1 protein 
      level and translocation in human monocytes in vitro. In addition, Hcy-induced 
      NADPH oxidase activity mediated the upregulation of Ref-1. Furthermore, 
      overexpressed Ref-1 upregulated NF-kappaB and MCP-1 promoter activity, and 
      antisense Ref-1 reduced Hcy-induced NF-kappaB DNA-binding activity and MCP-1 
      secretion. These data indicate that Hcy-induced ROS upregulate the expression and 
      translocation of Ref-1 via NADPH oxidase, and then Ref-1 increases NF-kappaB 
      activity and MCP-1 secretion in human monocytes/macrophages, which may accelerate 
      the development of atherosclerosis.
CI  - Copyright 2006 Elsevier Inc.
FAU - Dai, Jing
AU  - Dai J
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Science, 
      Peking University, Beijing 100083, People's Republic of China.
FAU - Li, Wenjing
AU  - Li W
FAU - Chang, Lina
AU  - Chang L
FAU - Zhang, Zhenmin
AU  - Zhang Z
FAU - Tang, Chaoshu
AU  - Tang C
FAU - Wang, Nanping
AU  - Wang N
FAU - Zhu, Yi
AU  - Zhu Y
FAU - Wang, Xian
AU  - Wang X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060830
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Apolipoproteins E)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 53-59-8 (NADP)
RN  - EC 4.2.99.18 (APEX1 protein, human)
RN  - EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase)
SB  - IM
MH  - Animals
MH  - Aorta/drug effects/metabolism/pathology
MH  - Apolipoproteins E/genetics
MH  - Atherosclerosis/etiology/immunology/*pathology
MH  - Chemokine CCL2/analysis/genetics/*metabolism
MH  - DNA-(Apurinic or Apyrimidinic Site) Lyase/analysis/*metabolism
MH  - Diet
MH  - Female
MH  - Foam Cells/chemistry/metabolism
MH  - Homocysteine/administration & dosage
MH  - Humans
MH  - Hyperhomocysteinemia/complications/*metabolism
MH  - Macrophages, Peritoneal/chemistry/drug effects/*metabolism
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Monocytes/chemistry/drug effects/metabolism
MH  - NADP/metabolism
MH  - NF-kappa B/agonists
MH  - Promoter Regions, Genetic/drug effects
MH  - Protein Transport
MH  - Reactive Oxygen Species/*metabolism
EDAT- 2006/10/19 09:00
MHDA- 2007/02/03 09:00
CRDT- 2006/10/19 09:00
PHST- 2006/01/12 00:00 [received]
PHST- 2006/08/21 00:00 [revised]
PHST- 2006/08/23 00:00 [accepted]
PHST- 2006/10/19 09:00 [pubmed]
PHST- 2007/02/03 09:00 [medline]
PHST- 2006/10/19 09:00 [entrez]
AID - S0891-5849(06)00544-2 [pii]
AID - 10.1016/j.freeradbiomed.2006.08.020 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2006 Nov 15;41(10):1566-77. doi: 
      10.1016/j.freeradbiomed.2006.08.020. Epub 2006 Aug 30.