Dietary omega-3 fatty acids alter cardiac mitochondrial phospholipid composition and delay Ca2+-induced permeability transition.
Consumption of omega-3 fatty acids from fish oil, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), decreases risk for heart failure and attenuates pathologic cardiac remodeling in response to pressure overload. Dietary supplementation with EPA + DHA may also impact cardiac mitochondrial function and energetics through alteration of membrane phospholipids. We assessed the role of EPA + DHA supplementation on left ventricular (LV) function, cardiac mitochondrial membrane phospholipid composition, respiration, and sensitivity to mitochondrial permeability transition pore (MPTP) opening in normal and infarcted myocardium. Rats were subjected to sham surgery or myocardial infarction by coronary artery ligation (n=10-14), and fed a standard diet, or supplemented with EPA + DHA (2.3% of energy intake) for 12 weeks. EPA + DHA altered fatty acid composition of total mitochondrial phospholipids and cardiolipin by reducing arachidonic acid content and increasing DHA incorporation. EPA + DHA significantly increased calcium uptake capacity in both subsarcolemmal and intrafibrillar mitochondria from sham rats. This treatment effect persisted with the addition of cyclosporin A, and was not accompanied by changes in mitochondrial respiration or coupling, or cyclophilin D protein expression. Myocardial infarction resulted in heart failure as evidenced by LV dilation and contractile dysfunction. Infarcted LV myocardium had decreased mitochondrial protein yield and activity of mitochondrial marker enzymes, however respiratory function of isolated mitochondria was normal. EPA + DHA had no effect on LV function, mitochondrial respiration, or MPTP opening in rats with heart failure. In conclusion, dietary supplementation with EPA + DHA altered mitochondrial membrane phospholipid fatty acid composition in normal and infarcted hearts, but delayed MPTP opening only in normal hearts.
O'Shea
Karen M
KM
Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
Khairallah
Ramzi J
RJ
Sparagna
Genevieve C
GC
Xu
Wenhong
W
Hecker
Peter A
PA
Robillard-Frayne
Isabelle
I
Des Rosiers
Christine
C
Kristian
Tibor
T
Murphy
Robert C
RC
Fiskum
Gary
G
Stanley
William C
WC
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002308:Cardiolipins / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D004452:Echocardiography; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
D002308:Cardiolipins; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010743:Phospholipids; D013481:Superoxides; D016572:Cyclosporine; D002118:Calcium
Biochim Biophys Acta. 2006 Sep-Oct;1757(9-10):1330-7
16697347
Circulation. 2003 Jun 3;107(21):2646-52
12782616
Am J Pathol. 2006 Dec;169(6):1913-24
17148657
Am J Physiol Heart Circ Physiol. 2007 Mar;292(3):H1498-506
17114240
Am J Clin Nutr. 2007 May;85(5):1222-8
17490956
J Pharmacol Exp Ther. 2009 Sep;330(3):670-8
19509316
J Pharmacol Exp Ther. 2007 May;321(2):707-15
17312185
Hypertension. 2009 Sep;54(3):605-11
19597033
Cell Death Differ. 2007 Jul;14(7):1243-7
17431425
J Mol Cell Cardiol. 2006 Dec;41(6):998-1009
17064727
J Am Coll Cardiol. 2005 Jun 21;45(12):2015-21
15963403
Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):e20-30
12588785
J Lipid Res. 2005 Jun;46(6):1196-204
15772420
J Neurochem. 2003 Sep;86(5):1101-7
12911618
J Lipid Res. 1986 Jan;27(1):114-20
3958609
J Mol Cell Cardiol. 2008 Apr;44(4):694-700
18328500
Cardiovasc Res. 2008 Oct 1;80(1):30-9
18710878
J Mol Cell Cardiol. 2009 Jun;46(6):850-7
19233198
J Cardiovasc Pharmacol. 2009 Apr;53(4):290-301
19276988
J Lipid Res. 2007 Jul;48(7):1559-70
17426348
Cardiovasc Res. 2009 Oct 1;84(1):33-41
19474179
J Mol Cell Cardiol. 2009 Jun;46(6):883-90
19265702
Nature. 2005 Mar 31;434(7033):658-62
15800627
Eur J Heart Fail. 2006 Nov;8(7):687-93
16513421
Lancet. 2008 Oct 4;372(9645):1223-30
18757090
J Biol Chem. 1977 Dec 10;252(23):8731-9
925018
J Biol Chem. 2004 Jun 11;279(24):25219-25
15070903
J Mol Cell Cardiol. 2009 Jun;46(6):821-31
19265700
J Mol Cell Cardiol. 2005 Jan;38(1):135-43
15623430
Am J Physiol. 1999 Jan;276(1):H149-58
9887028
Neurosci Lett. 1993 Nov 12;162(1-2):149-52
7907171
Prog Lipid Res. 2000 May;39(3):257-88
10799718
Cardiovasc Drugs Ther. 2006 Dec;20(6):425-32
17171295
FEBS Lett. 2006 Feb 6;580(3):775-81
16413540
Cardiovasc Res. 2007 Nov 1;76(2):303-10
17643403
Cardiovasc Res. 2008 Jul 15;79(2):331-40
18339649
J Biol Chem. 2006 Mar 17;281(11):6931-9
16407316
Am J Physiol. 1992 Nov;263(5 Pt 2):H1479-85
1332513
Toxicol Sci. 2005 Dec;88(2):495-504
16177237
J Mol Cell Cardiol. 2000 Dec;32(12):2361-7
11113011
Am J Physiol Cell Physiol. 2007 Jan;292(1):C33-44
16899548
Cardiovasc Res. 2009 Feb 1;81(2):319-27
19015135
J Mol Cell Cardiol. 2009 Mar;46(3):420-30
19094991
J Am Coll Cardiol. 2008 Sep 16;52(12):988-96
18786479
J Biol Chem. 2007 Jun 1;282(22):16623-30
17409097
Mol Cell Biochem. 1997 Nov;176(1-2):179-89
9406160