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Gli omega-3 prevengono la fibrosi cardiaca

La presentazione riguarda due studi diversi ma che hanno in comune l'uso degli acidi grassi omega-3 nello scompenso cardiaco. Già il ben noto GISSI-HF aveva dimostrato l'effetto positivo degli omega-3, attribuendolo in larga misura all'azione antiaritmica. Sembra pero' che non sia tutto qui. I due studi pubblicati su JACC e Circulation dimostrano che l'azione degli omega-3 è molto più complessa e riguarda non solo l'elettrofisiologia, ma anche la capacità funzionale del cuore. Secondo l'articolo di Circulation, l'azione principale degli omega-3 è ascrivibile ad una marcata prevenzione della fibrosi cardiaca, causa principale di disfunzione diastolica. Dallo studio su JACC si evince che la somministrazione di omega-3, anche nelle fasi iniziali di scompenso cardiaco da cardiomiopatia dilatativa, migliora la funzione sistolica ed ha il rimarchevole effetto clinico di riduzione dell'ospedalizzazione per scompenso. Gli acidi grassi omega-e sembrerebbero dunque possedere, oltre all'azione di stabilizzazione di membrana, cui si attribuisce l'effetto antiaritmico, anche un'azione sul rimodellamento cardiaco.

Omega-3 fatty acids prevent pressure overload-induced cardiac fibrosis through activation of cyclic GMP/protein kinase G signaling in cardiac fibroblasts

Chen J, Shearer GC, Chen Q, Healy CL, Beyer AJ, Nareddy VB, Gerdes AM, Harris WS, O'Connell TD, Wang D.

Circulation 2011;123:584-93

BACKGROUND: Omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) from fish oil ameliorate cardiovascular diseases. However, little is known about the effects of ?-3 polyunsaturated fatty acids on cardiac fibrosis, a major cause of diastolic dysfunction and heart failure. The present study assessed the effects of ?-3 polyunsaturated fatty acids on cardiac fibrosis.
METHODS AND RESULTS: We assessed left ventricular fibrosis and pathology in mice subjected to transverse aortic constriction after the consumption of a fish oil or a control diet. In control mice, 4 weeks of transverse aortic constriction induced significant cardiac dysfunction, cardiac fibrosis, and cardiac fibroblast activation (proliferation and transformation into myofibroblasts). Dietary supplementation with fish oil prevented transverse aortic constriction-induced cardiac dysfunction and cardiac fibrosis and blocked cardiac fibroblast activation. In heart tissue, transverse aortic constriction increased active transforming growth factor-ß1 levels and phosphorylation of Smad2. In isolated adult mouse cardiac fibroblasts, transforming growth factor-ß1 induced cardiac fibroblast transformation, proliferation, and collagen synthesis. Eicosapentaenoic acid and docosahexaenoic acid increased cyclic GMP levels and blocked cardiac fibroblast transformation, proliferation, and collagen synthesis. Eicosapentaenoic acid and docosahexaenoic acid blocked phospho-Smad2/3 nuclear translocation. DT3, a protein kinase G inhibitor, blocked the antifibrotic effects of eicosapentaenoic acid and docosahexaenoic acid. Eicosapentaenoic acid and docosahexaenoic acid increased phosphorylated endothelial nitric oxide synthase and endothelial nitric oxide synthase protein levels and nitric oxide production.
CONCLUSION: Omega-3 fatty acids prevent cardiac fibrosis and cardiac dysfunction by blocking transforming growth factor-ß1-induced phospho-Smad2/3 nuclear translocation through activation of the cyclic GMP/protein kinase G pathway in cardiac fibroblasts.

Circulation 2011;123:584-93

Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy

Nodari S, Triggiani M, Campia U, Manerba A, Milesi G, Cesana BM, Gheorghiade M, Dei Cas L.

J Am Coll Cardiol 2011;57:870-9

BACKGROUND: One hundred thirty-three patients with NICM and minimal symptoms on standard therapy were randomized to 2 g of n-3 PUFAs or placebo. LV function and functional capacity were assessed prospectively by echocardiography and cardiopulmonary exercise testing at baseline and at 12 months after randomization.
METHODS: Patients with chronic HF due to NICM and minimal symptoms while receiving evidence-based therapy were enrolled. LV function and functional capacity were assessed prospectively by echocardiography, cardiopulmonary exercise test, and New York Heart Association functional class at baseline and at 12 months after randomization to either 2 g of n-3 PUFAs or placebo.
RESULTS: At 12 months after randomization, the n-3 PUFAs group and the placebo group differed significantly (p <0.001) in regard to: 1) LV ejection fraction (increased by 10.4% and decreased by 5.0%, respectively); 2) peak VO(2) (increased by 6.2% and decreased by 4.5%, respectively); 3) exercise duration (increased by 7.5% and decreased by 4.8%, respectively); and 4) mean New York Heart Association functional class (decreased from 1.88 ± 0.33 to 1.61 ± 0.49 and increased from 1.83 ± 0.38 to 2.14 ± 0.65, respectively). The hospitalization rates for HF were 6% in the n-3 PUFAs and 30% in the placebo group (p = 0.0002).
CONCLUSIONS: In patients with NICM and minimal symptoms in response to evidence-based medical therapy, n-3 PUFAs treatment increases LV systolic function and functional capacity and may reduce hospitalizations for HF. Given these promising results, larger studies are in order to confirm our findings.

J Am Coll Cardiol 2011;57:870-9