Document Detail

NADPH oxidases in heart failure: poachers or gamekeepers?
MedLine Citation:
PMID:  22747566     Owner:  NLM     Status:  MEDLINE    
SIGNIFICANCE: Oxidative stress is involved in the pathogenesis of heart failure but clinical antioxidant trials have been unsuccessful. This may be because effects of reactive oxygen species (ROS) depend upon their source, location, and concentration. Nicotinamide adenine dinucleotide phosphate oxidase (Nox) proteins generate ROS in a highly regulated fashion and modulate several components of the heart failure phenotype.
RECENT ADVANCES: Two Nox isoforms, Nox2 and Nox4, are expressed in the heart. Studies using gene-modified mice deficient in Nox2 activity indicate that Nox2 activation contributes to angiotensin II-induced cardiomyocyte hypertrophy, atrial fibrillation, and the development of interstitial fibrosis but may also positively modulate physiological excitation-contraction coupling. Nox2 contributes to myocyte death under stress situations and plays important roles in postmyocardial infarction remodeling, in part by modulating matrix metalloprotease activity. In contrast to Nox2, Nox4 is constitutively active at a low level and induces protective effects in the heart under chronic stress, for example, by maintaining myocardial capillary density. However, high levels of Nox4 could have detrimental effects.
CRITICAL ISSUES: The effects of Nox proteins during the development of heart failure likely depend upon the isoform, activation level, and cellular distribution, and may include beneficial as well as detrimental effects. More needs to be learnt about the precise regulation of abundance and biochemical activity of these proteins in the heart as well as the downstream signaling pathways that they regulate.
FUTURE DIRECTIONS: The development of specific approaches to target individual Nox isoforms and/or specific cell types may be important for the achievement of therapeutic efficacy in heart failure.
Min Zhang; Alessia Perino; Alessandra Ghigo; Emilio Hirsch; Ajay M Shah
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2012-08-27
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  18     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-15     Completed Date:  2013-08-09     Revised Date:  2014-03-28    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1024-41     Citation Subset:  IM    
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MeSH Terms
Aldosterone / physiology
Angiotensin II / physiology
Arrhythmias, Cardiac / enzymology,  etiology
Enzyme Activation
Fibroblasts / enzymology
Heart Failure / drug therapy,  enzymology*,  pathology
Hydrogen Peroxide / metabolism
Hypertrophy, Left Ventricular / enzymology,  etiology
Leukocytes / enzymology
Membrane Glycoproteins / deficiency,  physiology
Models, Cardiovascular
Molecular Targeted Therapy
Myocytes, Cardiac / enzymology
NADPH Oxidase / antagonists & inhibitors,  deficiency,  genetics,  physiology*
Neovascularization, Pathologic / etiology
Oxidative Stress
Protein Isoforms
Reactive Oxygen Species
Subcellular Fractions / enzymology
Grant Support
RE/08/003//British Heart Foundation; RG/08/011/25922//British Heart Foundation; //Department of Health
Reg. No./Substance:
0/Membrane Glycoproteins; 0/Protein Isoforms; 0/Reactive Oxygen Species; 11128-99-7/Angiotensin II; 4964P6T9RB/Aldosterone; BBX060AN9V/Hydrogen Peroxide; EC protein, mouse; EC Oxidase

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

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