Treatment with Docosahexaenoic Acid, but Not Eicosapentaenoic Acid, Delays Ca²⁺-Induced Mitochondria Permeability Transition in Normal and Hypertrophied Myocardium

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 ϩ 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 ϩ 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 ϳ2-fold in both normal and hypertrophied hearts and increased EPA. DHA ϩ 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 2ϩ -induced MPTP opening was delayed by DHA and DHA ϩ 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 ϩ EPA offers no advantage over DHA alone.

EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4

“…DHA has known effects in the TAC model, including inhibition of mitochondrial transition pore opening ( 45,46 ), but whether this improves survival is not clear ( 45 ). Our data suggest that EPA-mediated prevention of fi brosis does not completely reverse diastolic dysfunction ( Fig.…”

Mitofusin-2 Maintains Mitochondrial Structure and Contributes to Stress-Induced Permeability Transition in Cardiac Myocytes

“…MPTP opening was inferred from the sudden and large increase of fluorescence. Mitochondrial Ca 2ϩ tolerance was defined as the cumulative Ca 2ϩ load that was required to induce the abrupt increase in extramitochondrial Ca 2ϩ from a semilog plot (47).…”

A 9-wk docosahexaenoic acid-enriched supplementation improves endurance exercise capacity and skeletal muscle mitochondrial function in adult rats

“…Their effects have been studied on cardiac and skeletal muscles, but with limited focus on mitochondrial function. It has been reported that n-3 polyunsaturated fatty acids increase cardiac mitochondrial calcium retention capacity without any change in oxygen consumption (32,45). However, the combination of DHA and EPA and the use of marine oil have been reported to have less profound effect compared with DHA alone (33).…”