A natural p300-specific HAT inhibitor, curcumin, possesses beneficial effects in addition to ACE inhibitor after rat myocardial infarction

A natural p300-specific HAT inhibitor, curcumin, possesses beneficial effects in addition to ACE inhibitor after rat myocardial infarction

Tatsuya Morimoto1, Yoichi Sunagawa1, Hiromichi Wada1, Tomohide Takaya1, Shigeki Yanagi2, Akihiro Sugimoto2, Masaki Tsukashita2, Akira Marui2, Tadashi Ikeda2, Masatoshi Fujita3, Akira Shimatsu1, Toru Kita4, Koji Hasegawa1.

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

The 17th Asian Pacific Congress of Cardiology (Kyoto, Japan), 2009/05/21 (Poster).

Abstract

Background: Recently we found that a natural compound, curcumin, which possesses p300 histone acetyltransferase inhibitory action, prevents the deterioration of systolic function in two heart failure models in rats. To apply this novel therapy in the clinical setting, it should be clarified whether curcumin possesses additional effects on a conventional therapy by angiotensin converting enzyme inhibitors (ACEI).

Objective: The purpose of this study is to examine the effect of ACEI/curcumin combination therapy on heart failure after myocardial infarction (MI).

Methods: On week after coronary ligation, 32 rats were randomly assigned to treatment with curcumin (50 mg/kg/day), enalapril (ACEI, 10 mg/kg/day), curcumin plus enalapril, or their solvents (control) for 6 weeks.

Results: There were no differences among 4 groups in all data examined before treatment. After treatment, LV fractional shortening (FS) was significantly higher in the ACEI group (29.0%) and in the curcumin group (28.7%) than the vehicle group (21.6%). Notably, LVFS significantly (p < 0.05) increased by ACEI/curcumin combination therapy (34.7%) compared with therapy by either ACEI or curcumin. LV wall thickness and cardiomyocyte diameter were significantly smaller in the ACEI/curcumin than the ACEI group.

Conclusions: A natural compound, curcumin, had beneficial effects on LV systolic function in addition to ACEI after rat MI. Thus, this non-toxic dietary compound will be applicable for heart failure therapy in the clinical setting.