Marine n3 polyunsaturated fatty acids enhance resistance to mitochondrial permeability transition in heart failure but do not improve survival

作者：Galvao Tatiana F; Khairallah Ramzi J; Dabkowski Erinne R; Brown Bethany H; Hecker Peter A; O'Connell Kelly A; O'Shea Karen M; Sabbah Hani N; Rastogi Sharad; Daneault Caroline; Des Rosiers Christine; Stanley William C^*

来源：American Journal of Physiology - Heart and Circulatory Physiology, 2013, 304(1): H12-H21.

DOI：10.1152/ajpheart.00657.2012

• cardiomyopathy
• diet
• fish oil
• metabolism
• mitochondria

Galvao TF, Khairallah RJ, Dabkowski ER, Brown BH, Hecker PA, O'Connell KA, O'Shea KM, Sabbah HN, Rastogi S, Daneault C, Des Rosiers C, Stanley WC. Marine n3 polyunsaturated fatty acids enhance resistance to mitochondrial permeability transition in heart failure but do not improve survival. Am J Physiol Heart Circ Physiol 304:H12-H21, 2013. First published October 26, 2012; doi:10.1152/ajpheart.00657.2012.-Mitochondrial dysfunction in heart failure includes greater susceptibility to mitochondrial permeability transition (MPT), which may worsen cardiac function and decrease survival. Treatment with a mixture of the n3 polyunsaturated fatty acids (n3 PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is beneficial in heart failure patients and increases resistance to MPT in animal models. We assessed whether DHA and EPA have similar effects when given individually, and whether they prolong survival in heart failure. Male delta-sarcoglycan null cardiomyopathic hamsters were untreated or given either DHA, EPA, or a 1:1 mixture of DHA + EPA at 2.1% of energy intake. Treatment did not prolong survival:mean survival was 298 +/- 15 days in untreated hamsters and 335 +/- 17, 328 +/- 14, and 311 +/- 15 days with DHA, EPA, and DHA + EPA, respectively (n = 27-32/group). A subgroup of cardiomyopathic hamsters treated for 26 wk had impaired left ventricular function and increased cardiomyocyte apoptosis compared with normal hamsters, which was unaffected by n3 PUFA treatment. Evaluation of oxidative phosphorylation in isolated subsarcolemmal and interfibrillar mitochondria with substrates for complex I or II showed no effect of n3 PUFA treatment. On the other hand, interfibrillar mitochondria from cardiomyopathic hamsters were significantly more sensitive to Ca2+-induced MPT, which was completely normalized by treatment with DHA and partially corrected by EPA. In conclusion, treatment with DHA or EPA normalizes Ca2+-induced MPT in cardiomyopathic hamsters but does not prolong survival or improve cardiac function. This suggest that greater susceptibility to MPT is not a contributor to cardiac pathology and poor survival in heart failure.

• 出版日期2013-1