Polyunsaturated fatty acids and their effects on cardiovascular disease

Abstract

Dietary polyunsaturated fatty acids (PUFAs) affect a wide variety of physiological processes. Much attention has been given to the n-3 PUFAs and their role in the prevention and treatment of cardiovascular disease, stemming from evidence obtained through a number of epidemiological studies and clinical trials. Investigators are now focused on elucidating the pathways and mechanisms for the biological action of n-3 PUFAs. Dietary intervention is recognized as a key measure in patient therapy and in the maintenance of human health in general. This review provides a summary of several important clinical trials, and while the exact modes of action of n-3 PUFA are not known, current viewpoints regarding the mechanisms of these fatty acids on atherosclerosis, circulating lipid profile, cell membranes, cell proliferation, platelet aggregation and cardiac arrhythmias are discussed.

Keywords: Arrhythmias; Atherosclerosis; Cardiovascular disease; Diet; Polyunsaturated fatty acids.

Figure 1)

The structure of two essential fatty acids – linoleic acid and alpha-linolenic acid

Figure 2)

The metabolic pathways of n-6 and n-3 polyunsaturated fatty acids. Metabolism of the two fatty acid families requires competition for the same elongation and desaturation enzymes. Note that the desaturation steps tend to be slow and rate-limiting compared with the more rapid elongation steps. Eicosanoids, such as prostaglandins, leukotrienes and thromboxanes, can be derived from arachidonic acid (AA) and eicosapentaenoic acid (EPA), and can mediate different physiological actions. ALA Alpha-linolenic acid; DHA Docosahexaenoic acid; LA Linoleic acid

Figure 3)

The major ion channels and transporters in a myocardial cell. The Na⁺/Ca²⁺ exchanger (NCX) and sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA) are normally responsible for Ca²⁺ extrusion following each contraction (A), but during ischemia (B), lack of O₂ limits ATP production and, thus, the function of the Na⁺/K⁺ ATPase (NAK) and SERCA. Uptake of Ca²⁺ by SERCA is inhibited and the NCX functions in reverse to compensate and removes Na⁺, but brings Ca²⁺ into the cell, resulting in Ca²⁺ overload and subsequent contracture and/or potentially lethal arrhythmias. [Ca²⁺]_i intracellular Ca²⁺ concentration; NAK Na⁺, K⁺ ATPase; RyR ryanodine receptor