Document Detail


Iron chelation inhibits the development of pulmonary vascular remodeling.
MedLine Citation:
PMID:  22974762     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Reactive oxygen species (ROS) have been implicated in the pathogenesis of pulmonary hypertension. Because iron is an important regulator of ROS biology, this study examined the effects of iron chelation on the development of pulmonary vascular remodeling. The administration of an iron chelator, deferoxamine, to rats prevented chronic hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling. Various iron chelators inhibited the growth of cultured pulmonary artery smooth muscle cells. Protein carbonylation, an important iron-dependent biological event, was promoted in association with pulmonary vascular remodeling and cell growth. A proteomic approach identified that Rho GDP-dissociation inhibitor (a negative regulator of RhoA) is carbonylated. In human plasma, the protein carbonyl content was significantly higher in patients with idiopathic pulmonary arterial hypertension than in healthy controls. These results suggest that iron plays an important role in the ROS-dependent mechanism underlying the development of pulmonary hypertension.
Authors:
Chi-Ming Wong; Ioana R Preston; Nicholas S Hill; Yuichiro J Suzuki
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-25
Journal Detail:
Title:  Free radical biology & medicine     Volume:  53     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-15     Completed Date:  2013-03-04     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1738-47     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Proteins / metabolism
Case-Control Studies
Cell Proliferation / drug effects
Cells, Cultured
Deferoxamine / pharmacology*,  therapeutic use
Female
Humans
Hydralazine / pharmacology
Hypertension, Pulmonary / blood,  physiopathology,  prevention & control
Iron Chelating Agents / pharmacology*,  therapeutic use
Male
Middle Aged
Myocardial Contraction / drug effects
Myocytes, Smooth Muscle / drug effects,  metabolism
Oxidation-Reduction
Protein Carbonylation
Pulmonary Artery / drug effects,  pathology,  physiopathology
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Vasodilator Agents / pharmacology
rho Guanine Nucleotide Dissociation Inhibitor alpha / metabolism
Grant Support
ID/Acronym/Agency:
R01 HL072844/HL/NHLBI NIH HHS; R01 HL097514/HL/NHLBI NIH HHS; R01HL72844/HL/NHLBI NIH HHS; R01HL97514/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Blood Proteins; 0/Iron Chelating Agents; 0/Reactive Oxygen Species; 0/Vasodilator Agents; 0/rho Guanine Nucleotide Dissociation Inhibitor alpha; 70-51-9/Deferoxamine; 86-54-4/Hydralazine
Comments/Corrections

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