Crucumin, a natural p300-specific histone acetyltransferase inhibitor, prevents the development of heart failure in vivo

Crucumin, a natural p300-specific histone acetyltransferase inhibitor, prevents the development of heart failure in vivo

Tatsuya Morimoto, Yoichi Sunagawa, Tomohide Takaya, Koji Hasegawa, Masatoshi Fujita, Toru Kita.

The 24th Annual Meeting of the International Society for Heart Research (Ferrara, Italy), 2007/06/21 (Talk).

Abstract

Purpose: We have found that curcumin inhibits p300, an intrinsic histone acetyltransferase (HAT)-induced acetylation of histones and GATA-4, and represses phenylephrine-induced hypertrophic responses in primary cardiac myocytes from neonatal rats in culture. To determine whether curcumin can prevent the development of heart failure in vivo, we have utilized a salt-sensitive Dahl (DS) rat model of hypertension and myocardial infarction (MI) rat model.

Methods: (1) We randomized 11-week-old DS rats with compensated concentric hypertrophy (n=56) to oral chronic daily treatment with curcumin (50 mg/kg/day) or vehicle. (2) One week after ligation, 32 rats with moderate-sized MI were randomly subjected to treatment with either curcumin (50 mg/kg/day) or vehicle.

Results: At the age of 17 weeks DS rats, curcumin significantly ameliorated the survival rate (curcumin: 76%, vehicle: 44%, p < 0.001). Curcumin treatment preserved LV fractional shortening both in 17-week-old DS rats (curcumin: 48%, vehicle: 31%, p < 0.05) and in MI rats at 7 weeks after ligation (curcumin: 30%, vehicle: 15%, p < 0.0001). Curcumin can suppress increases in acetylation of GATA4 and myocardial cell diameter in rat heats.

Conclusion: A natural compound, curcumin, an inhibitor p300-HAT activity, can prevent the development of heart failure in vivo. Thus, this compound might be applicable to heart failure therapy in humans.

Keywords: Histone acetyltransferase; p300; Heart failure