Novel heart failure therapy targeting transcriptional pathway in cardiomyocytes by a natural compound, curcumin

Abstract

Hypertensive heart disease and post-myocardial-infarction heart failure (HF) are leading causes of cardiovascular mortality in industrialized countries. To date, pharmacological agents that block cell surface receptors for neurohor-monal factors have been used, but despite such conventional therapy, HF is increasing in incidence worldwide. During the development and deterioration process of HF, cardiomyocytes undergo maladaptive hypertrophy, which markedly influences their gene expression. Regulation of histone acetylation by histone acetyltransferase (eg, p300) and histone deacetylase plays an important role in this process. Increasing evidence suggests that the excessive acetylation of cardiomyocyte nuclei is a hallmark of maladaptive cardiomyocyte hypertrophy. Curcumin inhibits p300-mediated nuclear acetylation, suggesting its usefulness in HF treatment. Clinical application of this natural compound, which is inexpensive and safe, should be established in the near future.