Abstract P344: A Natural p300-Specific Histone Acetyltransferase Inhibitor, Curcumin, Prevents the Development of Heart Failure in Addition to ACE Inhibitor After Myocardial Infarction in Rats
Background: We found that curcumin, a p300 histone acetyltransferase (HAT) inhibitor, prevents deterioration of the systolic function in rat heart failure models in vivo. To clinically apply this novel therapy to humans, it should be clarified whether or not curcumin has additional effects on conventional heart failure therapy comprising angiotensin-converting enzyme inhibitors (ACEI).
Methods and Results: Rats were subjected to a sham operation or myocardial infarction (MI). One week later, 32 rats were randomly assigned to solvents (control), enalapril (ACEI, 10 mg/kg/day) alone, curcumin (50 mg/kg/day) alone, or curcumin plus enalapril for 6 weeks. ACEI, but not curcumin treatment, decreased the blood pressure in post-MI rats. After treatment, LVFS (fractional shortening) was significantly (p<0.05) higher in the ACEI (29%) and curcumin (29%) groups than in the vehicle group (22%). Notably, LVFS significantly (p <0.05) increased on ACEI/ curcumin combination therapy (35%) compared with therapy comprising either ACEI or curcumin alone. The LV wall thickness and cardiomyocyte diameter were significantly smaller in the ACEI/curcumin than the ACEI group. Moreover, perivascular fibrosis was significantly reduced in the ACEI and curcumin groups compared with the vehicle group. This reduction was further augmented by the ACEI/ curcumin combination therapy.
Conclusion: Curcumin, restores the post-MI LV systolic function in rats without affecting the blood pressure. This natural non-toxic dietary compound in addition to ACEI has beneficial effects on LV systolic function.
- © 2011 by American Heart Association, Inc.