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. 2013 Dec;27(6):499-510.
doi: 10.1007/s10557-013-6487-4.

Docosahexaenoic acid supplementation alters key properties of cardiac mitochondria and modestly attenuates development of left ventricular dysfunction in pressure overload-induced heart failure

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Docosahexaenoic acid supplementation alters key properties of cardiac mitochondria and modestly attenuates development of left ventricular dysfunction in pressure overload-induced heart failure

Erinne R Dabkowski et al. Cardiovasc Drugs Ther. 2013 Dec.

Abstract

Purpose: Supplementation with the n3 polyunsaturated fatty acid docosahexaenoic acid (DHA) is beneficial in heart failure patients, however the mechanisms are unclear. DHA is incorporated into membrane phospholipids, which may prevent mitochondrial dysfunction. Thus we assessed the effects of DHA supplementation on cardiac mitochondria and the development of heart failure caused by aortic pressure overload.

Methods: Pathological cardiac hypertrophy was generated in rats by thoracic aortic constriction. Animals were fed either a standard diet or were supplemented with DHA (2.3 % of energy intake).

Results: After 14 weeks, heart failure was evident by left ventricular hypertrophy and chamber enlargement compared to shams. Left ventricle fractional shortening was unaffected by DHA treatment in sham animals (44.1 ± 1.6 % vs. 43.5 ± 2.2 % for standard diet and DHA, respectively), and decreased with heart failure in both treatment groups, but to a lesser extent in DHA treated animals (34.9 ± 1.7 %) than with the standard diet (29.7 ± 1.5 %, P < 0.03). DHA supplementation increased DHA content in mitochondrial phospholipids and decreased membrane viscosity. Myocardial mitochondrial oxidative capacity was decreased by heart failure and unaffected by DHA. DHA treatment enhanced Ca(2+) uptake by subsarcolemmal mitochondria in both sham and heart failure groups. Further, DHA lessened Ca(2+)-induced mitochondria swelling, an index of permeability transition, in heart failure animals. Heart failure increased hydrogen peroxide-induced mitochondrial permeability transition compared to sham, which was partially attenuated in interfibrillar mitochondria by treatment with DHA.

Conclusions: DHA decreased mitochondrial membrane viscosity and accelerated Ca(2+) uptake, and attenuated susceptibility to mitochondrial permeability transition and development of left ventricular dysfunction.

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Figures

Fig. 1
Fig. 1
Left ventricular mass and fractional shortening after 14 weeks of treatment. * P <0.05 compared to respective sham. # P <0.05 compared to untreated heart failure group. Groups sizes were 15 and 20 for the untreated sham and heart failure groups, respectfully, and 14 and 20 for the DHA treated sham and heart failure groups, respectfully
Fig. 2
Fig. 2
Top panels : activity of mitochondrial enzymes in whole LV tissue homogenates. Bottom panels: mitochondrial yields for SSM and IFM. *P <0.05 compared to sham animals within the dietary treatment
Fig. 3
Fig. 3
Phospholipid content of DHA (top panels) and arachidonic acid (bottom panels ) in SSM and IFM expressed as a percent of total fatty acids. Data are mean ± SEM. * P <0.001 compared to the respective untreated group. † P <0.05 compared to untreated sham group
Fig. 4
Fig. 4
Fluorescence polarization of 1,6 diphenyl 1,3,5 hexatriene in SSM and IFM, which reflects mitochondrial membrane viscosity. Groups sizes were 15 and 20 for the untreated sham and heart failure groups, respectfully, and 14 and 20 for the DHA treated sham and heart failure groups, respectfully
Fig. 5
Fig. 5
Change in absorbance at 540 nm, an index of LV mitochondrial swelling, following addition of 100 nmol Ca2+/mg mitochondrial protein. *P <0.05 for the DHA treated heart failure group compared to untreated heart failure; ^ P <0.05 for untreated sham compared to untreated heart failure. Groups sizes were 15 and 20 for the untreated sham and heart failure groups, respectfully, and 14 and 20 for the DHA treated sham and heart failure groups, respectfully
Fig. 6
Fig. 6
Extramitochondrial Ca2+ fluorescence. * P <0.05 heart failure compared to respective sham, # P <0.05 DHA treatment compared to standard diet in heart failure, ^ P <0.05 DHA treatment compared to standard diet in the sham groups. Groups sizes were 15 and 20 for the untreated sham and heart failure groups, respectfully, and 14 and 20 for the DHA treated sham and heart failure groups, respectfully
Fig. 7
Fig. 7
Time course of extramitochondrial Ca2+ fluorescence during a progressive increase in tBH. Values are normalized to total Ca2+ buffered during the loading phase (Fig. 5). * P <0.05 heart failure compared to respective sham, #P <0.05 DHA treatment compared to standard diet in heart failure, ^ P <0.05 DHA treatment compared to standard diet in the sham groups. Groups sizes were 15 and 20 for the untreated sham and heart failure groups, respectfully, and 14 and 20 for the DHA treated sham and heart failure groups, respectfully

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