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

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.