Abstract
Intake of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevents heart failure; however, the mechanisms are unclear. Mitochondrial permeability transition pore (MPTP) opening contributes to myocardial pathology in cardiac hypertrophy and heart failure, and treatment with DHA + EPA delays MPTP opening. Here, we assessed: 1) whether supplementation with both DHA and EPA is needed for optimal prevention of MPTP opening, and 2) whether this benefit occurs in hypertrophied myocardium. Rats with either normal myocardium or cardiac hypertrophy induced by 8 weeks of abdominal aortic banding were fed one of four diets: control diet without DHA or EPA or diets enriched with either DHA, EPA, or DHA + EPA (1:1 ratio) at 2.5% of energy intake for 17 weeks. Aortic banding caused a 27% increase in left ventricular mass and 25% depletion in DHA in mitochondrial phosopholipids in rats fed the control diet. DHA supplementation raised DHA in phospholipids ∼2-fold in both normal and hypertrophied hearts and increased EPA. DHA + EPA supplementation also increased DHA, but to a lesser extent than DHA alone. EPA supplementation increased EPA, but did not affect DHA compared with the control diet. Ca2+-induced MPTP opening was delayed by DHA and DHA + EPA supplementation in both normal and hypertrophied hearts, but EPA had no effect on MPTP opening. These results show that supplementation with DHA alone effectively increases both DHA and EPA in cardiac mitochondrial phospholipids and delays MPTP and suggest that treatment with DHA + EPA offers no advantage over DHA alone.
Footnotes
This work was supported by the National Institutes of Health National Heart, Lung, and Blood Institute [Grants HL074237, HL091307, HL101434].
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.170605.
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ABBREVIATIONS:
- DHA
- docosahexaenoic acid
- EPA
- eicosapentaenoic acid
- ARA
- arachidonic acid
- MPTP
- mitochondrial permeability transition
- PUFA
- polyunsaturated fatty acids
- CTRL
- control
- AAB
- abdominal aortic banding
- LV
- left ventricle
- MHC
- myosin heavy chain
- ANF
- atrial natriuretic factor
- BSA
- bovine serum albumin
- SSM
- subsarcolemmal mitochondria
- IFM
- interfibrillar mitochondria
- MOPS
- 4-morpholinepropanesulfonic acid
- RCR
- respiratory control ratio.
- Received May 26, 2010.
- Accepted July 9, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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