α-Linolenic Acid-Enriched Diet Prevents Myocardial Damage and Expands Longevity in Cardiomyopathic Hamsters
α-Linolenic Acid-Enriched Diet Prevents Myocardial Damage and Expands Longevity in Cardiomyopathic Hamsters
Year: 2006
Authors: Fiaccavento, R. Carotenuto, F. Minieri, M. Masuelli, L. Vecchini, A. Bei, R. Modesti, A. et. al.
Publication Name: Am. J. Pathol.
Publication Details: Volume 169; Pages 1913 – 1924.
Abstract:
Randomized clinical trials have demonstrated that the increased intake of n3 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, gamma 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 beta 1) 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 n3polyunsaturated fatty acids are mainly related to preservation of myocardium structure and function and the attenuation of myocardial fibrosis. (Authors abstract)
N3 PUFAs exhibit positive effects on hemostatic factors, thrombogenesis, blood pressure, plasma lipids, and heart susceptibility to ventricular arrhythmias. No epidemiological or experimental studies have investigated their effects in hereditary cardiomyopathies. The present study was designed to test the hypothesis that n3 PUFAs could beneficially affect the pathophysiological mechanisms of hereditary cardiac hypertrophy. The UM-X7.1 hamster strain was used as the experimental model because this strain displays abnormal accumulation of n6 fatty acids in the heart and severely damaged cardiac mitochondrial and cellular membranes. These animals exhibit a cardiomyopathic phenotype associated with the deletion of the gamma sarcoglycan (gamma SG) gene. The aim of this study was to modulate the lipid composition of the hearts of cardiomyopathic hamsters (CMPHs) by administering an ALA enriched diet, in an attempt to attenuate cardiomyopathic structural and functional damages. ALA was chosen because the hamster�s capability to uptake, transport, and store this specific PUFA has been extensively investigated. The present study demonstrated that dietary ALA leads to a remarkable elongation of the survival of hamsters suffering from hereditary cardiomyopathy. This extended longevity is sustained by ALA protective effects on cardiac cells and on cardiac tissue structure and function against damage induced by gamma-SG ablation1and mitochondrial gene mutation. Such protection was achieved by administering ALA to CMPH from weaning to death. The extended longevity of CMPH/FS is directly related to the increased intake of ALA, which targeted the myocardium, as demonstrated by a massive presence in plasma and heart. Adult CMPH/PT cardiac tissue lipids were enriched in linoleic and arachidonic acid, compared with age-matched GSH/PT. The ALA-enriched diet (after weaning) may have slowed the effects of lipogenic enzyme dysregulation, thus preserving normal cardiac lipid composition. The presence of the sarcoglycan complex in membranes is crucial in stabilizing the transmembrane bridge. According to the authors, the observations concerning CMPH/FS cardiomyocytes sugest that maintaining an adequate n3/n6 balance is necessary in preserving the plasmalemma�s mechanical features, as demonstrated by the expression and proper alignment of membrane proteins involved in cell contacts and signaling. Additional beneficial mechanisms in CMPH/FS hearts may be due to the massive presence of ALA and EPA and the relatively low AA content. Collectively, the ALA-enriched diet counteracted the CMPH�s potential derangement of cardiac tissue texture and function. CMPH/FS hearts exhibited preserved myofibrillar spatial organization and intracardiomyocyte signalling. CMPH/FS also displayed hemodynamic indices similar to those of GSH/PT, due to suitable ventricular muscle area proportion, the meager fibrosis, and the high cardiomyocyte mechanical efficiency and energy availability. The effects of dietary ALA on cardiomyopathic hamsters culminated in a postponement of cardiac failure and an extension of their longevity: by the time all CMPH/PT perished, more than 60% of CMPH fed with flaxseeds were still alive and apparently in good health. The data thus suggest that ALA can be used to successfully prevent the cardiac damage of hereditary diseases and that this preventive treatment is very efficient, safe, and economically advantageous. In cardiomyopathic hamsters, the pathogenesis of the disease seems to result from the complex interplay between genetic and environmental factors. An ALA enriched diet delays fibrosis, preserves heart performance, and induces a marked prolongation of the cardiomyopathic hamster�s longevity. (Editors comments)
N3 PUFAs exhibit positive effects on hemostatic factors, thrombogenesis, blood pressure, plasma lipids, and heart susceptibility to ventricular arrhythmias. No epidemiological or experimental studies have investigated their effects in hereditary cardiomyopathies. The present study was designed to test the hypothesis that n3 PUFAs could beneficially affect the pathophysiological mechanisms of hereditary cardiac hypertrophy. The UM-X7.1 hamster strain was used as the experimental model because this strain displays abnormal accumulation of n6 fatty acids in the heart and severely damaged cardiac mitochondrial and cellular membranes. These animals exhibit a cardiomyopathic phenotype associated with the deletion of the gamma sarcoglycan (gamma SG) gene. The aim of this study was to modulate the lipid composition of the hearts of cardiomyopathic hamsters (CMPHs) by administering an ALA enriched diet, in an attempt to attenuate cardiomyopathic structural and functional damages. ALA was chosen because the hamster�s capability to uptake, transport, and store this specific PUFA has been extensively investigated. The present study demonstrated that dietary ALA leads to a remarkable elongation of the survival of hamsters suffering from hereditary cardiomyopathy. This extended longevity is sustained by ALA protective effects on cardiac cells and on cardiac tissue structure and function against damage induced by gamma-SG ablation1and mitochondrial gene mutation. Such protection was achieved by administering ALA to CMPH from weaning to death. The extended longevity of CMPH/FS is directly related to the increased intake of ALA, which targeted the myocardium, as demonstrated by a massive presence in plasma and heart. Adult CMPH/PT cardiac tissue lipids were enriched in linoleic and arachidonic acid, compared with age-matched GSH/PT. The ALA-enriched diet (after weaning) may have slowed the effects of lipogenic enzyme dysregulation, thus preserving normal cardiac lipid composition. The presence of the sarcoglycan complex in membranes is crucial in stabilizing the transmembrane bridge. According to the authors, the observations concerning CMPH/FS cardiomyocytes sugest that maintaining an adequate n3/n6 balance is necessary in preserving the plasmalemma�s mechanical features, as demonstrated by the expression and proper alignment of membrane proteins involved in cell contacts and signaling. Additional beneficial mechanisms in CMPH/FS hearts may be due to the massive presence of ALA and EPA and the relatively low AA content. Collectively, the ALA-enriched diet counteracted the CMPH�s potential derangement of cardiac tissue texture and function. CMPH/FS hearts exhibited preserved myofibrillar spatial organization and intracardiomyocyte signalling. CMPH/FS also displayed hemodynamic indices similar to those of GSH/PT, due to suitable ventricular muscle area proportion, the meager fibrosis, and the high cardiomyocyte mechanical efficiency and energy availability. The effects of dietary ALA on cardiomyopathic hamsters culminated in a postponement of cardiac failure and an extension of their longevity: by the time all CMPH/PT perished, more than 60% of CMPH fed with flaxseeds were still alive and apparently in good health. The data thus suggest that ALA can be used to successfully prevent the cardiac damage of hereditary diseases and that this preventive treatment is very efficient, safe, and economically advantageous. In cardiomyopathic hamsters, the pathogenesis of the disease seems to result from the complex interplay between genetic and environmental factors. An ALA enriched diet delays fibrosis, preserves heart performance, and induces a marked prolongation of the cardiomyopathic hamster�s longevity. (Editors comments)
