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

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 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

Omega-3 fatty acid supplementation and cardiovascular disease

“…The impact on intracellular calcium handling is particularly noteworthy. Stanley et al ( 177,179,180 ) recently identifi ed the mitochondrial permeability transition pore (MPTP) as a target for 3 PUFA regulation. MPTP is a large-diameter, high-conductance, voltagedependent channel that allows passage of water, ions, and molecules up to 1.5 kDa.…”

“…Findings that dietary SDA lowers some infl ammatory markers suggest this dietary source of 3 PUFA will be useful in modulating infl ammatory factors linked to CVD. DHA, however, has a greater capacity to regulate cardiac mitochondrial MPTP than other 3 PUFA ( 177,179,180 ). This is important for ventricular fi brillation and SCD ( 177,180,(230)(231)(232).…”

“…DHA, however, has a greater capacity to regulate cardiac mitochondrial MPTP than other 3 PUFA ( 177,179,180 ). This is important for ventricular fi brillation and SCD ( 177,180,(230)(231)(232). Whether SDA supplementation can affect SCD remains to be determined through more investigation.…”

Mitochondrial Free Radicals, Antioxidants, Nutrient Substances, and Chronic Hepatitis C

“…In addition, IFN-a and ribavirin treatment can further lead to EPA depletion . Supplementation with DHA alone or both DHA and EPA significantly delays Ca 2+ -induced MPTP opening in normal and hypertrophied myocardium (O'Shea et al, 2009;Khairallah et al, 2010). These changes were accompanied by an increase in DHA and EPA level in mitochondrial phospholipids and decreased AA level (Khairallah et al, 2010).…”

“…Cardiolipin is composed of four linoleic acid side chains, which is essential for normal mitochondrial respiration; however, substitute such as long chain saturated and monounsaturated fatty acids weaken mitochondrial function (O'Shea et al, 2009). Recent study has shown that increased saturated fatty acids and cholesterol associated with alteration in mitochondrial membrane and cardiolipin oxidation, which are required for HCV replication (Roe et al, 2011).…”