Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids

January 1, 2010 Human Health and Nutrition Data 0 Comments

Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids

Year: 2010
Authors: Adkins, Y. Kelley, D.S.
Publication Name: Journal of Nutritional Biochemistry
Publication Details: Volume 21; Pages 781 – 792.


Typical omega 3 polyunsaturated fatty acids (n-3 PUFAs) are docosahexaenoic acid and eicosapentaenoic acid in the form of fish oils andα linolenic acid from flaxseed oil. Epidemiological studies suggested the benefits of n-3 PUFA on cardiovascular health. Intervention studies confirmed that the consumption of n-3 PUFA provided benefits for primary and secondary prevention of cardiovascular disease. Evidence from cellular and molecular research studies indicates that the cardioprotective effects of n-3 PUFA result from a synergism between multiple, intricate mechanisms that involve anti-inflammation, proresolving lipid mediators, modulation of cardiac ion channels, reduction of triglycerides, influence on membrane microdomains and downstream cell signaling pathways and antithrombotic and antiarrhythmic effects. n-3 PUFAs inhibit inflammatory signaling pathways (nuclear factor-κ B activity) and down-regulate fatty acid (FA) synthesis gene expression (sterol regulatory element binding protein-1c) and up-regulate gene expression involved in FA oxidation (peroxisome proliferator-activated receptor α). This review examines the various mechanisms by which n-3 PUFA exert beneficial effects against CVD. (Author�s abstract)
This article describes research on the cardioprotective effects of fish oils and of individual omega 3 polyunsaturated fatty acids (n-3 PUFA), or more specifically, eicosapentaenoic acid (EPA; 20:5 n-3), docosahexaenoic acid (DHA; 22:6 n-3) and α-linolenic acid (ALA; 18:3 n-3). Many large-scale studies, including primary and secondary prevention clinical trials and meta-analysis of cohorts, have concluded that consumption of fatty fish, fish oils or individual n-3 PUFA is an effective dietary strategy to lower CVD morbidity, mortality, as well as classic and emerging risk factors. In addition, n-3 PUFA have been shown to improve a number of cardiac hemodynamic factors such as blood pressure, left ventricular diastolic filling, heart rate and endothelial function. The cardioprotective effects of n-3 PUFA also include arrhythmia prevention, plasma triacylglycerol reduction, vascular relaxation improvement, anti-inflammatory responses, platelet aggregation inhibition, enhancement of plaque stability and anti-atherosclerotic effects. Consumption of high amounts of saturated fatty acid (SFA), trans fatty acid (FA) and omega-6 (n-6) PUFA and low amounts of n-3PUFA (approx n-6:n-3 PUFA ratio of 16:1) is a pattern often observed in a typical Western diet. This is very different from the pattern found in the ancestoral diets who had a n-6:n-3 PUFA ratio of ~1. Cells must adapt to this surplus (n-6) and deficiency of (n-3) specific dietary PUFA. n-3 and n-6 PUFAs regulate a number of transcription factors and interact with nuclear receptors such as peroxisome proliferator-activated receptors (PPARs), liver X receptor (LXR), hepatocyte nuclear factor-4α, nuclear factor-κB (NFκB) and sterol regulatory element binding protein (SREBP), all of which influence inflammatory responses and lipid metabolism. An imbalance of dietary n-6:n-3 PUFA ratio may result in altered gene regulation and expression in downstream pathways resulting in altered protein expression and activity that can negatively affect cell membrane composition and fluidity and organ function. The cardioprotective effects of n-3 PUFA appear to be due to a synergism between multiple, intricate mechanisms that involve TG lowering, anti-inflammatory, inflammation-resolving, regulation of transcription factors and gene expression, membrane fluidity and antiarrhythmic and antithrombotic effects. Further research on the overlapping and independent mechanisms by which n-3 prevent and reverse CVD is suggested. (Editor�s comments)

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