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(American Journal of Pathology. 2006;169:1913-1924.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.051320

{alpha}-Linolenic Acid-Enriched Diet Prevents Myocardial Damage and Expands Longevity in Cardiomyopathic Hamsters

Roberta Fiaccavento*{dagger}, Felicia Carotenuto*{dagger}, Marilena Minieri*{dagger}, Laura Masuelli{ddagger}, Alba Vecchini§, Roberto Bei, Andrea Modesti, Luciano Binaglia§, Angelo Fusco||, Aldo Bertoli||, Giancarlo Forte**, Luciana Carosella{dagger}{dagger} and Paolo Di Nardo*{dagger}

From the Laboratorio di Cardiologia Molecolare e Cellulare* and Medicina Molecolare,|| the Dipartimento di Medicina Interna, and the Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Roma Tor Vergata, Roma; the Istituto Nazionale per la Ricerca Cardiovascolare,{dagger} Bologna; the Dipartimento di Medicina Sperimentale e Patologia,{ddagger} Università di Roma la Sapienza, Roma; the Dipartimento di Medicina Interna,§ Sezione di Biochimica, Università di Perugia, Perugia; Syntech srl,** Roma; and the Istituto di Medicina Interna e Geriatria,{dagger}{dagger} Università Cattolica S. Cuore, Roma, Italy

Randomized clinical trials have demonstrated that the increased intake of {omega}-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, {delta}-sarcoglycan-null cardiomyopathic hamsters were fed from weaning to death with an {alpha}-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-ß1) 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 {omega}-3 polyunsaturated fatty acids are mainly related to preservation of myocardium structure and function and the attenuation of myocardial fibrosis.




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