| Glucose 6-Phosphate Dehydrogenase Deficiency Increases Redox Stress and Moderately Accelerates the Development of Heart Failure. | |
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MedLine Citation:
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PMID: 23170010 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: -Glucose 6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency in the world. In failing hearts, G6PD is upregulated and generates NADPH that is used by the glutathione pathway to remove reactive oxygen species (ROS), but also as a substrate by ROS-generating enzymes. Therefore, G6PD deficiency might prevent heart failure by decreasing NADPH and ROS 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 LV dilation and dysfunction in both WT 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 LV dilation in G6PDX mice than WT. We further stressed TAC mice by feeding a high fructose diet to increase flux through G6PD and ROS production, and again observed worse LV remodeling and a lower ejection fraction in G6PDX than WT mice. Tissue content of lipid peroxidation products was increased in G6PDX mice in response to infarction and aconitase activity was decreased with TAC, 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 LV 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. |
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Authors:
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Peter A Hecker; Vincenzo Lionetti; Rogerio F Ribeiro; Sharad Rastogi; Bethany H Brown; Kelly A O'Connell; James W Cox; Kadambari C Shekar; Dionna Gamble; Hani N Sabbah; Jane A Leopold; Sachin A Gupte; Fabio A Recchia; William C Stanley |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-20 |
Journal Detail:
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Title: Circulation. Heart failure Volume: - ISSN: 1941-3297 ISO Abbreviation: Circ Heart Fail Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101479941 Medline TA: Circ Heart Fail Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 University of Maryland, Baltimore, MD; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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