Effects of trichostatin, a histone deacetylase inhibitor, on cardiomyocyte hypertrophy

Objective To investigate the effects of trichostatin (TSA) on neonatal rat cardiomyocyte hypertrophy induced by angiotensin Ⅱ (AngⅡ) infusion. Methods Primary cultured neonatal rat cardiomyocytes were treated with angiotensin Ⅱ with or in the absence of TSA pretreatment. Cardiomyocytes cross area, [3H] Leucine incorporation rate, as well as mRNA expression level of ANP and BNP, were measured. The protein expression level of acetylated histone H3 and phosphorylated JNK was also examined. Results The cardiomyocyte cross area enlarged to (1.63±0.46) times to the original, which was blunted by pretreatment of TSA at the dosage of 10-7 mmol/L and 3×10-7 mmol/L. Increased protein synthesis rates and upregulation of mRNA expression of ANP as well as BNP by AngⅡ stimulation, were also blocked by TSA treatment. The protein expressions of acetylated histone H3, as well as phosphorylated JNK were upregulated by AngⅡ induction, which were also inhibited by TSA. Conclusions TSA pretreatment blunts cardiomyocyte hypertrophy induced by Ang Ⅱ infusion, which is possibly due to the inhibition of total histone deacetylase (HDAC) activity and JNK activation. Key words: Heart failure; Histone deacetylase inhibitors; Histone deacetylases; Trichostatin