α-linolenic acid-enriched diet prevents myocardial damage and expands longevity in cardiomyopathic hamsters

Abstract

Randomized clinical trials have demonstrated that the increased intake of ω-3 polyunsaturated fatty acids significantly reduces the risk of ischemic cardiovascular disease, but no investigations have been performed in hereditary cardiomyopathies with diffusely damaged myocardium. In the present study, δ-sarcoglycan-null cardiomyopathic hamsters were fed from weaning to death with an α-linolenic acid (ALA)-enriched versus standard diet. Results demonstrated a great accumulation of ALA and eicosapentaenoic acid and an increased eicosapentaenoic/arachidonic acid ratio in cardiomyopathic hamster hearts, correlating with the preservation of myocardial structure and function. In fact, ALA administration preserved plasmalemma and mitochondrial membrane integrity, thus maintaining proper cell/extracellular matrix contacts and signaling, as well as a normal gene expression profile (myosin heavy chain isoforms, atrial natriuretic peptide, transforming growth factor-β1) and a limited extension of fibrotic areas within ALA-fed cardiomyopathic hearts. Consequently, hemodynamic indexes were safeguarded, and more than 60% of ALA-fed animals were still alive (mean survival time, 293 ± 141.8 days) when all those fed with standard diet were deceased (mean survival time, 175.9 ± 56 days). Therefore, the clinically evident beneficial effects of ω-3 polyunsaturated fatty acids are mainly related to preservation of myocardium structure and function and the attenuation of myocardial fibrosis. Copyright © American Society for Investigative Pathology.