Curcumin, a natural p300-specific HAT inhibitor, prevents heart failure
Tomohide Takaya.
Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
The 3rd SIRIC-NCVC Joint Symposium (Seoul, Korea), 2011/11/11 (Talk).
Abstract
Hemodynamic overload in the heart can trigger maladaptive hypertrophy of cardiomyocytes, which eventually leads to systolic dysfunction or decompensated heart failure. We have clarified that a histone acetyltransferase (HAT), p300, mediates nuclear acetylation during this process. HAT activity of p300 is required for the development of left ventricular remodeling after myocardial infarction. Therefore, inhibition of HAT activity of p300 is a possible therapeutic approach for heart failure.
Curcumin, a polyphenol included in spice turmeric, possesses HAT inhibitory activity with specificity for p300/CBP. We have been investigating whether curcumin can be used as a therapeutic agent for heart failure. In cultured cardiomyocytes, curcumin inhibited acetylation and DNA-binding of GATA4, a hypertrophy-responsive transcription factor. In vivo effects of curcumin for heart failure were examined in two different rat models; hypertensive heart disease and surgically induced myocardial infarction. Administration of curcumin prevented hypertrophy and deterioration of systolic function in both models. From these results, we conclude that inhibition of p300 HAT activity by curcumin, a nontoxic dietary compound, may provide a novel therapeutic strategy for heart failure in humans.