PMID- 20463304
OWN - NLM
STAT- MEDLINE
DCOM- 20100525
LR  - 20211020
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 235
IP  - 5
DP  - 2010 May
TI  - The iron chelator, desferrioxamine, reduces inflammation and atherosclerotic 
      lesion development in experimental mice.
PG  - 633-41
LID - 10.1258/ebm.2009.009229 [doi]
AB  - Vascular inflammation and monocyte recruitment are initiating events in 
      atherosclerosis that have been suggested to be caused, in part, by iron-mediated 
      oxidative stress and shifts in the intracellular redox environment of vascular 
      cells. Therefore, the objective of this study was to investigate whether the 
      intracellular iron chelator, desferrioxamine (DFO), reduces inflammation and 
      atherosclerosis in experimental mice. Treatment of C57BL/6J mice with DFO (daily 
      intraperitoneal injection of 100 mg/kg body weight for two weeks) strongly 
      inhibited lipopolysaccharide-induced increases of soluble cellular adhesion 
      molecules and monocyte chemoattractant protein-1 (MCP-1) in the serum and 
      activation of the redox-sensitive transcription factors, nuclear factor-kappaB 
      and activator protein-1, in the aorta. Furthermore, treatment of apolipoprotein 
      E-deficient (apoE-/-) mice with DFO (100 mg/kg, intraperitoneal, daily for 10 
      weeks) attenuated aortic atherosclerotic lesion development by 26% (P < 0.05). 
      DFO treatment of apoE-/- mice also lowered serum levels of MCP-1 and gene 
      expression of proinflammatory and macrophage markers in the aorta and heart, in 
      parallel with increased protein expression of the transferrin receptor in the 
      heart and liver. In contrast, DFO treatment had no effect on serum cholesterol 
      and triglyceride levels. These data show that DFO inhibits inflammation and 
      atherosclerosis in experimental mice, providing the proof-of-concept for an 
      important role of iron in atherogenesis. Whether eliminating excess iron is a 
      useful adjunct for the prevention or treatment of atherosclerosis in humans 
      remains to be investigated.
FAU - Zhang, Wei-Jian
AU  - Zhang WJ
AD  - Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. 
      weijian.zhang@oregonstate.edu
FAU - Wei, Hao
AU  - Wei H
FAU - Frei, Balz
AU  - Frei B
LA  - eng
GR  - P01 AT002034-04/AT/NCCIH NIH HHS/United States
GR  - P01 AT002034-02/AT/NCCIH NIH HHS/United States
GR  - P01 AT002034-03/AT/NCCIH NIH HHS/United States
GR  - P01 AT002034-06/AT/NCCIH NIH HHS/United States
GR  - P01 AT002034-07/AT/NCCIH NIH HHS/United States
GR  - P01 AT002034-05/AT/NCCIH NIH HHS/United States
GR  - P01 AT002034-077040/AT/NCCIH NIH HHS/United States
GR  - P01 AT002034-039001/AT/NCCIH NIH HHS/United States
GR  - P01 AT002034-019001/AT/NCCIH NIH HHS/United States
GR  - P01 AT002034/AT/NCCIH NIH HHS/United States
GR  - P01 AT002034-01/AT/NCCIH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Apolipoproteins E)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Iron Chelating Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Triglycerides)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - E1UOL152H7 (Iron)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Animals
MH  - Aorta/drug effects/metabolism/pathology
MH  - Apolipoproteins E/deficiency/metabolism
MH  - Atherosclerosis/blood/*complications/*drug therapy/pathology
MH  - Chemokine CCL2/blood
MH  - Cholesterol/metabolism
MH  - Deferoxamine/pharmacology/*therapeutic use
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Inflammation/*complications/*drug therapy/genetics/pathology
MH  - Intercellular Adhesion Molecule-1/blood
MH  - Iron/metabolism
MH  - Iron Chelating Agents/pharmacology/*therapeutic use
MH  - Lipopolysaccharides
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Organ Specificity/drug effects/genetics
MH  - Solubility/drug effects
MH  - Transcription Factor AP-1/metabolism
MH  - Triglycerides/metabolism
MH  - Vascular Cell Adhesion Molecule-1/blood
MH  - Weight Gain/drug effects
PMC - PMC3057189
MID - NIHMS187511
COIS- DISCLOSURE/CONFLICT OF INTEREST There is NO conflict of interest to disclose.
EDAT- 2010/05/14 06:00
MHDA- 2010/05/26 06:00
PMCR- 2011/03/15
CRDT- 2010/05/14 06:00
PHST- 2010/05/14 06:00 [entrez]
PHST- 2010/05/14 06:00 [pubmed]
PHST- 2010/05/26 06:00 [medline]
PHST- 2011/03/15 00:00 [pmc-release]
AID - 235/5/633 [pii]
AID - 10.1258/ebm.2009.009229 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2010 May;235(5):633-41. doi: 10.1258/ebm.2009.009229.