| Marine n3 polyunsaturated fatty acids enhance resistance to mitochondrial permeability transition in heart failure but do not improve survival. | |
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MedLine Citation:
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PMID: 23103493 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mitochondrial dysfunction in heart failure includes greater susceptibility to mitochondrial permeability transition (MPT), which may worsen cardiac function and decrease survival. Treatment with a mixture of the n3 polyunsaturated fatty acids (n3 PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is beneficial in heart failure patients and increases resistance to MPT in animal models. We assessed whether DHA and EPA have similar effects when given individually, and whether they prolong survival in heart failure. Male δ-sarcoglycan null cardiomyopathic hamsters were untreated or given either DHA, EPA, or a 1:1 mixture of DHA + EPA at 2.1% of energy intake. Treatment did not prolong survival: mean survival was 298 ± 15 days in untreated hamsters and 335 ± 17, 328 ± 14, and 311 ± 15 days with DHA, EPA, and DHA + EPA, respectively (n = 27-32/group). A subgroup of cardiomyopathic hamsters treated for 26 wk had impaired left ventricular function and increased cardiomyocyte apoptosis compared with normal hamsters, which was unaffected by n3 PUFA treatment. Evaluation of oxidative phosphorylation in isolated subsarcolemmal and interfibrillar mitochondria with substrates for complex I or II showed no effect of n3 PUFA treatment. On the other hand, interfibrillar mitochondria from cardiomyopathic hamsters were significantly more sensitive to Ca(2+)-induced MPT, which was completely normalized by treatment with DHA and partially corrected by EPA. In conclusion, treatment with DHA or EPA normalizes Ca(2+)-induced MPT in cardiomyopathic hamsters but does not prolong survival or improve cardiac function. This suggest that greater susceptibility to MPT is not a contributor to cardiac pathology and poor survival in heart failure. |
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Authors:
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Tatiana F Galvao; Ramzi J Khairallah; Erinne R Dabkowski; Bethany H Brown; Peter A Hecker; Kelly A O'Connell; Karen M O'Shea; Hani N Sabbah; Sharad Rastogi; Caroline Daneault; Christine Des Rosiers; William C Stanley |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural Date: 2012-10-26 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 304 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-01-02 Completed Date: 2013-02-20 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H12-21 Citation Subset: IM |
Affiliation:
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Division of Cardiology, Department of Medicine, University of Maryland, 20 Penn St., Baltimore, MD 21201, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Genetically Modified Apoptosis / drug effects Calcium / metabolism Cardiomyopathy, Dilated / drug therapy*, genetics, metabolism, pathology, physiopathology Cardiotonic Agents / pharmacology* Cricetinae Disease Models, Animal Docosahexaenoic Acids / pharmacology* Drug Therapy, Combination Eicosapentaenoic Acid / pharmacology* Heart Failure / drug therapy*, genetics, metabolism, pathology, physiopathology Male Mitochondria, Heart / drug effects*, metabolism, pathology Mitochondrial Membrane Transport Proteins / drug effects*, metabolism Myocytes, Cardiac / drug effects*, metabolism, pathology Oxidative Phosphorylation / drug effects Phospholipids / metabolism Sarcoglycans / deficiency, genetics Stroke Volume / drug effects Time Factors Ventricular Function, Left / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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HL-072751/HL/NHLBI NIH HHS; HL-074237/HL/NHLBI NIH HHS; HL-101434/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/Mitochondrial Membrane Transport Proteins; 0/Phospholipids; 0/Sarcoglycans; 0/mitochondrial permeability transition pore; 1553-41-9/Eicosapentaenoic Acid; 25167-62-8/Docosahexaenoic Acids; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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