Document Detail

Glucose 6-phosphate dehydrogenase deficiency increases redox stress and moderately accelerates the development of heart failure.
MedLine Citation:
PMID:  23170010     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Glucose 6-phosphate dehydrogenase (G6PD) is the most common deficient enzyme in the world. In failing hearts, G6PD is upregulated and generates reduced nicotinamide adenine dinucleotide phosphate (NADPH) that is used by the glutathione pathway to remove reactive oxygen species but also as a substrate by reactive oxygen species-generating enzymes. Therefore, G6PD deficiency might prevent heart failure by decreasing NADPH and reactive oxygen species production.
METHODS AND RESULTS: This hypothesis was evaluated in a mouse model of human G6PD deficiency (G6PDX mice, ≈40% normal activity). Myocardial infarction with 3 months follow-up resulted in left ventricular dilation and dysfunction in both wild-type and G6PDX mice but significantly greater end diastolic volume and wall thinning in G6PDX mice. Similarly, pressure overload induced by transverse aortic constriction (TAC) for 6 weeks caused greater left ventricular dilation in G6PDX mice than wild-type mice. We further stressed transverse aortic constriction mice by feeding a high fructose diet to increase flux through G6PD and reactive oxygen species production and again observed worse left ventricular remodeling and a lower ejection fraction in G6PDX than wild-type mice. Tissue content of lipid peroxidation products was increased in G6PDX mice in response to infarction and aconitase activity was decreased with transverse aortic constriction, suggesting that G6PD deficiency increases myocardial oxidative stress and subsequent damage.
CONCLUSIONS: Contrary to our hypothesis, G6PD deficiency increased redox stress in response to infarction or pressure overload. However, we found only a modest acceleration of left ventricular remodeling, suggesting that, in individuals with G6PD deficiency and concurrent hypertension or myocardial infarction, the risk for developing heart failure is higher but limited by compensatory mechanisms.
Peter A Hecker; Vincenzo Lionetti; Rogerio F Ribeiro; Sharad Rastogi; Bethany H Brown; Kelly A O'Connell; James W Cox; Kadambari C Shekar; Dionna M Gamble; Hani N Sabbah; Jane A Leopold; Sachin A Gupte; Fabio A Recchia; William C Stanley
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-20
Journal Detail:
Title:  Circulation. Heart failure     Volume:  6     ISSN:  1941-3297     ISO Abbreviation:  Circ Heart Fail     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-03-05     Revised Date:  2014-10-29    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  United States    
Other Details:
Languages:  eng     Pagination:  118-26     Citation Subset:  IM    
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MeSH Terms
Disease Models, Animal
Disease Progression
Glucosephosphate Dehydrogenase / metabolism*
Glucosephosphate Dehydrogenase Deficiency / complications*,  metabolism
Heart Failure / etiology*,  metabolism,  physiopathology
Lipid Peroxidation
Mice, Inbred C3H
Myocardium / enzymology*
Reactive Oxygen Species / metabolism
Ventricular Remodeling*
Grant Support
Reg. No./Substance:
0/Reactive Oxygen Species; EC Dehydrogenase

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

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