Document Detail


Antioxidants for the treatment of patients with severe angioproliferative pulmonary hypertension?
MedLine Citation:
PMID:  22870869     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SIGNIFICANCE: Pathobiological mechanisms that contribute to pulmonary vasoconstriction, lung vascular remodeling, and the development of right heart failure include the generation of reactive oxygen and nitrogen species and the response of lung vascular and cardiac cells to these molecules. We review the information regarding oxidant stress balanced by antioxidant mechanisms and the role of oxidants and antioxidants in hypoxic pulmonary hypertension and their potential role in an animal model of severe pulmonary arterial hypertension (PAH).
RECENT ADVANCES: In human lung tissue from patients with idiopathic PAH, we find reduced superoxide dismutase activity and high expression of the oxidant stress markers nitrotyrosine and 8-OH-guanosine. In the Sugen 5416/chronic hypoxia model of PAH, lung tissue expression of nitrotyrosine and hemeoxygenase 1 (HO-1) is substantial, while HO-1 expression in the failing right ventricle is decreased. This model, based on administration of the VEGF receptor blocker Sugen 5416 and chronic hypoxia (Su/Hx), reproduces many of the characteristic features of severe angioobliterative human PAH. Treatment of Su/Hx rats with protandim, which nuclear factor erythroid-2 related factor (Nrf2)-dependently upregulates the expression of genes encoding antioxidant enzymes, protects against right heart failure without affecting angioobliterative PAH.
CRITICAL ISSUES: In human severe PAH, patient survival is determined by the function of the stressed right ventricle; investigation of oxidative and nitrosative stresses and their potential contribution to right heart failure is necessary.
FUTURE DIRECTIONS: Antioxidant therapeutic strategies may be of benefit in the setting of human severe PAH. Whether antioxidant strategies affect lung vascular remodeling and/or prevent right heart failure remains to be examined.
Authors:
Norbert F Voelkel; Harm J Bogaard; Aysar Al Husseini; Laszlo Farkas; Jose Gomez-Arroyo; Ramesh Natarajan
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Publication Detail:
Type:  Journal Article; Review     Date:  2012-09-28
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  18     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-05     Completed Date:  2013-10-22     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1810-7     Citation Subset:  IM    
Affiliation:
Victoria Johnson Center for Lung Research, Virginia Commonwealth University, Richmond, VA 23298, USA. nvoelkel@mcvh-vcu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia
Antioxidants / therapeutic use*
Disease Models, Animal
Heart Failure / etiology
Heme Oxygenase-1 / metabolism
Humans
Hypertension, Pulmonary / complications,  drug therapy*,  etiology,  pathology
Lung / blood supply,  metabolism,  pathology
Mice
Neovascularization, Pathologic / drug therapy
Oxidative Stress
Rats
Superoxide Dismutase / metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; EC 1.14.99.3/Heme Oxygenase-1; EC 1.15.1.1/Superoxide Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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