| Thioredoxin 1 Is Essential for Sodium Sulfide-Mediated Cardioprotection in the Setting of Heart Failure. | |
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MedLine Citation:
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PMID: 23349187 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: The aim of this study was to determine whether thioredoxin 1 (Trx1) mediates the cardioprotective effects of hydrogen sulfide (H(2)S) in a model of ischemic-induced heart failure (HF).Approach and Results-Mice with a cardiac-specific overexpression of a dominant negative mutant of Trx1 and wild-type littermates were subjected to ischemic-induced HF. Treatment with H(2)S as sodium sulfide (Na(2)S) not only increased the gene and protein expression of Trx1 in the absence of ischemia but also augmented the HF-induced increase in both. Wild-type mice treated with Na(2)S experienced less left-ventricular dilatation, improved left-ventricular function, and less cardiac hypertrophy after the induction of HF. In contrast, Na(2)S therapy failed to improve any of these parameters in the dominant negative mutant of Trx1 mice. Studies aimed at evaluating the underlying cardioprotective mechanisms found that Na(2)S therapy inhibited HF-induced apoptosis signaling kinase-1 signaling and nuclear export of histone deacetylase 4 in a Trx1-dependent manner. CONCLUSIONS: These findings provide novel information that the upregulation of Trx1 by Na(2)S therapy in the setting of HF sets into motion events, such as the inhibition of apoptosis signaling kinase-1 signaling and histone deacetylase 4 nuclear export, which ultimately leads to the attenuationof left-ventricular remodeling. |
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Authors:
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Chad K Nicholson; Jonathan P Lambert; Jeffery D Molkentin; Junichi Sadoshima; John W Calvert |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-24 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: - ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, Atlanta, GA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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