Cytoprotection of Cardiac Myocytes by Polyunsaturated Fatty Acids

Summary

Most of the risk factors associated with cardiovascular disease can be controlled by nutrition. Polyunsaturated fatty acids (PUFA) of the 03C93 series are known for their beneficial effect on the risk, but can also influence the severity of cardiac disease through their direct action on the myocardium. Introducing ω3 PUFA in the diet results in a marked decrease of the AA/DHA ratio, mainly due to an increase in membrane DHA content. In several experimental models, such structural changes were reported to affect cardiac functions. Among them the membrane ω3 PUFA appear to affect the oxygen cost of energy production by decreasing the fatty acid beta-oxidation in cardiac myocytes, and the improved recovery of mitochondrial function in the post-ischemic heart of rats fed fish oil. On the other hand, the incorporation of DHA in cardiac myocyte membranes induces a large decrease in the biochemical response to catecholamine stimulation. Although the mechanism does not involve a direct modification of the adrenergic receptors, the consequences of DHA intake in vivo reduces heart rate and show some similarity with the cardiac effect of β-blockers. This observation could be correlated with the observations that which occurs during ischemia and reperfusion-induced arrhythmias are largely reduced when cardiac membranes contains 15–20% DHA. In addition, the presence of ω3 PUFAs in the membranes reduces the synthesis of Prostaglandines as in other organs. However, they can exert a fine-tuned control of myocardium prostaglandin synthesis in pathological conditions, since during hypoxia and reoxygenation, the effect of ω3 PUFAs becomes more specific to each prostaglandin, with no inhibition of the hypoxia-induced PGE2 synthesis, and a large inhibition of the reoxygenation-induced PGI2 release. The 3 mechanisms reported here may account for the significantly positive effects of dietary ω3 PUFAs reported in epidemiological studies. Each one contributes to cardiac protection in reference to a cardio-active drug (metabolic effectors, β-blockers, or aspirin), largely appreciated in the treatment of cardiac diseases.