FLAXSEED-ENRICHED DIET IN THE PROTECTION AGAINST BETA ADRENERGIC-INDUCED FIBROSIS AND HYPERTROPHY

The sympathetic system plays a pivotal role in the pathophysiology of heart remodelling and failure. In particular β-adrenergic stimulation leads to cardiac hypertrophy and fibrosis in cooperation with renin-angiotensin-aldosterone system and matrix metalloproteinase 2. In the rat Transforming Growth Factor b is reported to mediate cardiac fibrosis also when produced by repeated administrations of isoproterenol. An increased sympathetic activity takes place since the beginning of a heart failure, when it contributes to compensate cardiac output. Although initially beneficial, a long term increased adrenergic activity leads to a severe deterioration of cardiac performance. The a-linolenic acid (ALA) is reported to prevent myocardial damage and to expand longevity in genetically cardiomyopathic hamsters, as well as to prevent apoptosis of isolated hamster cardiomyocytes by counteracting the activity of Tumor Necrosis Factor a. Here we investigated whether ALA can prevent isoproterenol-induced fibrosis and hypertrophy in rats. Control rats (Group I; n = 6) were fed for ten weeks with normal diet without any treatment. Rats in Group II (n = 6) were fed with the same diet, but after the first week received 100 mg/day of isoproterenol by subcutaneous injection for five days. Rats in Group III (n = 7) were also treated with isoproterenol but were fed with a flaxseed-enriched diet during the entire period of observation. Then, after echocardiographical analysis, the animals were sacrificed and the hearts were explanted, weighted and studied with trichromic staining. Ecocardiography showed a significant decrease of ejection fraction in Group II with respect to Group I (p<0.01) and III (p<0.05). The weight of the hearts was higher in Group II (1.36±0.06SD g) with respect to Group I (1.04±0.14SD g; p<0.05) and Group III (1.07±0.14SD g; p<0.005). Finally, in Group II trichromic staining revealed the presence of an extensive fibrosis that was absent in the other two groups. It may be concluded that in rat hearts ALA supplementation in the diet completely prevents fibrosis, hypertrophy and mechanical impairment brought about by isoproterenol. Since ALA is present in several dietary sources, the supplementation could represent a powerful protective tool against the worsening of an initial heart failure.