Cardiac Membrane Polyunsaturated Fatty Acids as Therapeutic Targets in Age-Associated Heart Diseases

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Citation
Asia Pacific Cardiology - Volume 1 Issue 1;2007:1(1):17-19

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Modification of cardiac membrane lipid composition leads to functional changes in lipid–protein interactions and related metabolic processes that are a major factor underlying the reduced capacity to recover from acute injury or to adapt during chronic disease in advanced age.1 In addition to perturbed regulation of ion homeostasis, metabolic intermediates and antioxidant systems, important adaptive and maladaptive membrane phospholipid changes occur in ageing and age-related heart disease. We have previously reported that with advanced age there are increases in the omega (ω)-6 polyunsaturated fatty acids (PUFAs) and phosphatidylcholine, in contrast to decreases in ω-3 PUFAs and cardiolipin.2,3
A deficiency of long-chain ω-3 PUFAs in myocardial membranes has been proposed to underlie an increased vulnerability to cardiac arrhythmias in age-related cardiovascular disease. Phospholipids and their constituent fatty acids are integral to cell membrane function and to biologically active membrane-derived signalling products, including fatty acid diacylglycerols, inositol triphosphate and fatty acid metabolites. Many PUFAs are required in the diet as mammals cannot synthesise them de novo.4,5 Of the two main families, ω-6 PUFAs are readily available in the diet as linoleic acid (LA). The main PUFAs in myocardial membranes are the ω-6 PUFAs, LA and arachidonic acid (AA), and the ω-3 PUFA docosahexaenoic acid (DHA).
With abundant LA and high levels of ω-6 PUFA in the ‘modern’ diet of developed nations, α-linolenic acid (ALA) cannot be converted to adequate levels of eicosapentaenoic acid (EPA) and DHA. This is due to competition for the desaturase enzymes with the vast excess of dietary ω-6 PUFA.4–8
Delta-5 and delta-6 fatty acid desaturases are crucial for the conversion of both ω-6 PUFAs (LA to AA) and ω-3 PUFA (ALA to EPA and DHA).4–8 The activity of microsomal delta-6 desaturase is lower than that of delta-5, making it the rate-limiting step involved in two stages of DHA production.8 Thus, in the face of a dietary intake that is low in ALA and high in LA and AA (e.g. meat), there is usually a reduction in ω-3 PUFA content in membranes; this is exacerbated by any downturn in desaturase enzyme function.5,6

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