An increased sympathetic discharge affects the heart since the early stage of a failure. If initially it compensates the reduced cardiac output, its long term effect results in myocardial fibrosis and hypertrophy with worsening of the failure. The damage can be prevented by ω-3 fatty acids. such as docosahexaenoic (DHA), eicosapenaenoic (EPA) and α-linolenic acid (ALA) (1,2). While DHA and EPA are found in fishes, ALA is present in various vegetables included flaxseeds. A flaxseed enriched diet is reported to prevent the appearance of myocardial fibrosis in d-sarcoglycan-null cardiomyopatic hamsters (2). We studied whether this diet can prevent myocardial fibrosis and hypertrophy in rats treated with isoproterenol (ISO). Wistar rats were divided in 3 groups: Control group (CTR; n=7) after 7 days of acclimatization rats underwent a daily subcutaneous injection of saline (0.5 ml) for 5 days and were fed with a standard pellet chow; ISO group (n=7+7) rats received 100 mg/kg of ISO instead of saline and were fed as CTR; ISO+ALA group (n=7) rats received ISO, but were fed with an ALA enriched diet before, during and after ISO. For all groups the observation lasted 60 days after the end of ISO treatment. Then surviving rats were anaesthetized with peritoneal injection of ketamine (100 mg/kg) and xylazine (5 mg/kg), heparinised (200 IU) and decapitated. The hearts were excised and weighted. Data are expressed as means±SD. One-way ANOVA was used. Seven rats of ISO group died during treatment. Thus 7 additional rats were added to have the same number of hearts to examine in all groups. ALA enriched diet prevented the ISO-induced death. Heart/body weight ratio was 0.32±0.2% in CTR. It increased in ISO group to 0.41±0.15% (p<0.01), while it was unchanged in ISO+ALA. In ISO group, histology (n=4 each group in triplicate) revealed a remarkable production and deposition of collagen, with an increase in the cross sectional area of myocytes from 199±3 µm² in the CTR to 250±10 µm² (p<0.001). NO change was observed in ISO+ALA. Western blot analysis (n= 3 each group in triplicate) showed the following changes in ISO group with respect to CTR: 4 time increase (p<0.001) of Transforming Growth Factor-ß (TGF-ß) expression; reduction by about 25% (p<0.05) of Tissue inhibitor of metalloproteinase 1 (TIMP1) expression; increase by more than 3 times of ß-myosin concentration (p<0.001). The changes were not observed in ISO+ALA. Zymography revealed that the activity of both latent and active forms of Metalloproteinase2 (MMP2) increased by about 50% (p<0.05 and p<0.001 respectively) in ISO group. In conclusion, ALA prevents cardiac fibrosis by abolishing the changes in TGF-ß, TIMP1 and MMP2 expression induced by ß-adrenergic hyperactivity. Moreover, since hypertrophy is related to the increase of TGF-ß, it is likely that its prevention by ALA takes place by limiting the expression of this cytokine. [ABSTRACT FROM AUTHOR]