Treatment with docosahexaenoic acid, but not eicosapentaenoic acid, delays Ca2+-induced mitochondria permeability transition in normal and hypertrophied myocardium.
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 phospholipids 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. Ca(2+)-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.
Khairallah
Ramzi J
RJ
Division of Cardiology and Department of Medicine, University of Maryland, Baltimore, MD 21201, USA.
O'Shea
Karen M
KM
Brown
Bethany H
BH
Khanna
Nishanth
N
Des Rosiers
Christine
C
Stanley
William C
WC
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000378:metabolism*; D004032:Diet; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000494:pharmacology*; D004562:Electrocardiography; D005227:Fatty Acids / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism; D014463:Ultrasonography
D005227:Fatty Acids; D010743:Phospholipids; D012333:RNA, Messenger; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D002118:Calcium