Abstract 16031: Docosahexaenoic Acid Prevents Cardiac Dysfunction in Heart Failure, and Increases Mitochondrial Membrane Fluidity, Ca2+ Uptake, and Resistance to Permeability Transition
Treatment with docosahexaenoic acid (DHA, 22:6n3), a marine n-3 polyunsaturated fatty acid, has protective effects in patients and rodent models of heart failure (HF), however the mechanism of these effects are unclear. We found that dietary intake of DHA dramatically alters mitochondrial membrane composition in the heart. Here, we determined the mitochondrial effects of DHA supplementation in aortic pressure overload-induced HF. Rats were subjected to transverse aortic constriction (TAC) and were assigned to either no DHA or DHA at 2.3% of energy intake (equivalent to ∼4 g/day in humans). After 14 weeks, LV mass increased by ∼48% with TAC, with no effect of DHA treatment. LV ejection was decreased in TAC animals compared to Sham (Figure). Assessment of isolated mitochondria revealed that DHA accelerated mitochondrial Ca2+uptake (Figure), and attenuated Ca2+-induced mitochondrial swelling, a measure of permeability transition (P<0.05). DHA had no effects on mitochondrial capacity for oxidative phosphorylation or mitochondrial coupling (P:O ratio or State 4 respiration) with lipid and non-lipid substrates. In conclusion, DHA treatment significantly prevented deterioration of LV function, which was associated with accelerated mitochondrial Ca2+uptake and resistance to permeability transition, which may be responsible for the improved LV function.
- © 2012 by American Heart Association, Inc.