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

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

Yoichi Sunagawa1, Tatsuya Morimoto1, Teruhisa Kawamura1, Tomohide Takaya1, Shoichi Miyamoto2, Hiromichi Wada1, Akira Shimatsu3, Masatoshi Fujita1, Toru Kita4, Koji Hasegawa1.

  1. Division of Translational Reseaarch, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  2. Department of Cardiovascular Medicine, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan
  3. Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  4. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

第11回日本心不全学会学術集会 (千葉), 2007/09/10 (ポスター).

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 weeks 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 weeks 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).

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.