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Issue 7, 2015
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Alpha-linolenic acid protects against cardiac injury and remodelling induced by beta-adrenergic overstimulation

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Abstract

We investigated the effect of α-linolenic acid (ALA) in protecting the heart from injury caused by β-adrenergic overstimulation. ALA's role either in isoproterenol (ISO)-treated isolated rat cardiomyocytes (H9c2 cells) or in in vivo rat hearts was studied. In isolated cardiomyocytes in vitro, the involvement of kinases (Src and PI3K) in protection was tested using the specific inhibitors (PP2 or LY294002 respectively), while the role of caveolae was assessed by their disruption with methyl-β-cyclodextrin. The rats underwent either a normal chow diet or, alternatively, an ALA-enriched diet before, during and throughout the 60 days after 5 days of isoproterenol administration. Before sacrifice, the hemodynamic changes were measured using echocardiography. In the explanted hearts, histological changes together with molecular markers of cardiac fibrosis and hypertrophy were evaluated. In H9c2 cells, ALA abolished the ISO-induced reduction of viability. This effect was suppressed by both the inhibitor PP2 or LY294002 and the caveolae disrupter methyl-β-cyclodextrin. In the rats, ALA prevented ISO-induced myocardial fibrosis and hypertrophy and kept the cardiac mechanical function as in the control. It also counteracted the increased expressions of transforming growth factor-β (TGF-β) and β-myosin (β-MHC), the decreased expression of tissue inhibitor metalloproteinase-1 (TIMP-1) and the enhanced activity of matrix metalloproteinase-2 (MMP-2). In conclusion, ALA-induced protection requires the integrity of caveolae where β2-adrenergic receptors (β2ARs) are restricted and mediate the activation of the Src-PI3K protective pathway. By preserving this β2AR pro-survival pathway, an ALA-enriched diet protects the heart against ISO-induced fibrosis and hypertrophy.

Graphical abstract: Alpha-linolenic acid protects against cardiac injury and remodelling induced by beta-adrenergic overstimulation

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Publication details

The article was received on 12 Jan 2015, accepted on 22 May 2015 and first published on 22 May 2015


Article type: Paper
DOI: 10.1039/C5FO00034C
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Food Funct., 2015,6, 2231-2239

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    Alpha-linolenic acid protects against cardiac injury and remodelling induced by beta-adrenergic overstimulation

    A. Folino, A. E. Sprio, F. Di Scipio, G. N. Berta and R. Rastaldo, Food Funct., 2015, 6, 2231
    DOI: 10.1039/C5FO00034C

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