A natural p300-specific histone acetyltransferase inhibitor, curcumin, in addition to angiotensin-converting enzyme inhibitor, exerts beneficial effects on left ventricular systolic function after myocardial infarction in rats

Circ J. 2011;75(9):2151-9. doi: 10.1253/circj.cj-10-1072. Epub 2011 Jul 8.

Abstract

Background: A natural p300-specific histone acetyltransferase (HAT) inhibitor, curcumin, may have therapeutic potential for heart failure. However, it is unclear whether curcumin exhibits beneficial additive or synergistic effects on conventional therapy with angiotensin-converting enzyme inhibitors (ACEIs).

Methods and results: Rats were subjected to a sham operation or left coronary artery ligation. One week later, 34 rats with a moderate sized myocardial infarction (MI) were randomly assigned to 4 groups: solvents as control (n = 8), enalapril (an ACEI, 10 mg·kg⁻¹·day⁻¹) alone (n=8), curcumin (50 mg·kg⁻¹·day⁻¹) alone (n = 9) and enalapril plus curcumin (n = 9). Daily oral treatment was repeated and continued for 6 weeks. Echocardiographic data were similar among the 4 groups before treatment. After treatment, left ventricular (LV) fractional shortening (FS) was significantly higher in the enalapril (29.0 ± 1.9%) and curcumin (30.8 ± 1.7%) groups than in the vehicle group (19.7 ± 1.6%). Notably, LVFS further increased in the enalapril/curcumin combination group (34.4 ± 1.8%). Histologically, cardiomyocyte diameter in the non-infarct area was smaller in the enalapril/curcumin combination group than in the enalapril group. Perivascular fibrosis was significantly reduced in the enalapril/curcumin group compared with the curcumin group.

Conclusions: A natural non-toxic dietary compound, curcumin, combined with an ACEI exerts beneficial effects on post-MI LV systolic function in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Curcumin / pharmacology*
  • E1A-Associated p300 Protein / antagonists & inhibitors*
  • Electrocardiography
  • Enalapril / pharmacology*
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology
  • Histone Deacetylase Inhibitors / pharmacology*
  • Male
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Systole
  • Ventricular Function, Left / drug effects*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Enalapril
  • E1A-Associated p300 Protein
  • Ep300 protein, rat
  • Curcumin