Best Abstract Award – Second prize
Topic: Heart Failure (Basic), Molecular Cardiology
A major morphogenic change in heart failure is the hypertrophy of individual cardiomyocytes. Suppressing cardiomyocytes hypertrophy enables the prevention and treatment of heart failure. Although many experimental studies and clinical intervention trials have shown the cardioprotective effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little is known about the effects of these acids on cardiomyocyte hypertrophy. This study investigated whether DHA and EPA inhibit cardiac hypertrophy, and compared the effects of EPA and DHA on cultured cardiomyocytes.
First, to compare the effects on hypertrophic responses, neonatal rat cultured cardiomyocytes were stimulated with 30 µM phenylephrine (PE) in the presence or absence of EPA or DHA. Palmitic acid and stearic acid were used as controls. After 48 hours, cardiomyocyte surface area, hypertrophic response gene transcription, and the ratio of acetylated histone H3 were measured. Next, an in vitro HAT assay was performed to determine the direct effect of EPA and DHA on p300-HAT activity.
Treatment with either DHA or EPA significantly inhibited PE-induced hypertrophic response including myofibrillar organisation, increase in cell size, and mRNA expression of ANF and BNP. Moreover, DHA and EPA repressed the PE-induced acetylation of histone-3 in cardiomyocytes to the same extent. The in vitro HAT assay revealed that EPA and DHA significantly inhibited p300-HAT activity.
These findings suggest that EPA and DHA repress PE-induced hypertrophic responses in cardiomyocytes to the same extent, through the direct inhibition of histone acetyltransferase activity.