A natural p300-specific histone acetyltransferase inhibitor, curcumin, prevents the development of hypertension-induced heart failure in salt-sensitive Dahl rats

A natural p300-specific histone acetyltransferase inhibitor, curcumin, prevents the development of hypertension-induced heart failure in salt-sensitive Dahl rats

Tatsuya Morimoto1, Yoichi Sunagawa2, Teruhisa Kawamura2, Tomohide Takaya2, Shoichi Miyamoto1, Hiromichi Wada2, Akira Shimatsu2, Masatoshi Fujita3, Toru Kita1, Koji Hasegawa2.

  1. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  2. Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  3. School of Health Sciences, Faculty of Medicine, Kyoto University, Kyoto, Japan.

第71回日本循環器学会学術集会 (神戸), 2007/03/17 (ポスター).

Abstract

Introduction: We have found that curcumin, a major curcumanoid isolated from Curcuma longa, inhibits p300, an intrinsic histone acetyltransferase (HAT), -induced hypertrophic responses in primary cardiac myocytes from neonatal rats in culture.

Objective: 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.

Methods: In this model, left ventricular (LV) compensated concentric hypertrophy at the age of 11 weeks is followed by decrease in systolic function at the age of 17 weeks. We randomized 11-week-old DS rat (n = 56) to oral chronic daily treatment with curcumin (50 mg/kg/day) or vehicle.

Results: At the age of 17 weeks, curcumin significantly ameliorated the survival rate (curcumin: 76%, vehicle: 44%, p < 0.001). However, blood pressure did not differ between curcumin- and vehicle-treated groups throughout the treatment period. Analysis of surviving rats at the age of 17 weeks demonstrates that curcumin treatment preserved LV fractional shortening (curcumin: 48%, vehicle: 31%, p < 0.05). In addition, the plasma BNP concentration in the curcumin-treated group was significantly (p < 0.05) lower than that in the control group.

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