Dietary ω-3 fatty acids alter cardiac mitochondrial phospholipid composition and delay Ca2+-induced permeability transition

O'Shea, Karen M.; Khairallah, Ramzi J.; Sparagna, Genevieve C.; Xu, Wenhong; Hecker, Peter A.; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Kristian, Tibor; Murphy, Robert C.; Fiskum, Gary; Stanley, William C.

doi:10.1016/j.yjmcc.2009.08.014

« Previous Next »Journal of Molecular and Cellular Cardiology
Volume 47, Issue 6 , Pages 819-827, December 2009

Dietary ω-3 fatty acids alter cardiac mitochondrial phospholipid composition and delay Ca²⁺-induced permeability transition

Karen M. O'Shea
- Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA
- Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA
Ramzi J. Khairallah
- Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA
Genevieve C. Sparagna
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA
Wenhong Xu
- Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA
Peter A. Hecker
- Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA
Isabelle Robillard-Frayne
- Department of Nutrition and Montreal Heart Institute, Université de Montréal, Montreal, Canada
Christine Des Rosiers
- Department of Nutrition and Montreal Heart Institute, Université de Montréal, Montreal, Canada
Tibor Kristian
- Department of Anesthesiology and Trauma and Anesthesiology Research Center, University of Maryland, Baltimore, MD, USA
Robert C. Murphy
- Department of Pharmacology, University of Colorado Denver and Health Sciences Center, Aurora, CO, USA
Gary Fiskum
- Department of Anesthesiology and Trauma and Anesthesiology Research Center, University of Maryland, Baltimore, MD, USA
William C. Stanley
- Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA
- Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA
- Corresponding author. Division of Cardiology, Department of Medicine, University of Maryland-Baltimore, 20 Penn Street, HSF2, Room S022, Baltimore, MD 21201, USA. Fax: +1 410 706 3583.

Received 24 June 2009; received in revised form 7 August 2009; accepted 12 August 2009. published online 25 August 2009.

Abstract

Consumption of ω-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.