Curcumin prevents and reverses murine cardiac hypertrophy

J Clin Invest. 2008 Mar;118(3):879-93. doi: 10.1172/JCI32865.

Abstract

Chromatin remodeling, particularly histone acetylation, plays a critical role in the progression of pathological cardiac hypertrophy and heart failure. We hypothesized that curcumin, a natural polyphenolic compound abundant in the spice turmeric and a known suppressor of histone acetylation, would suppress cardiac hypertrophy through the disruption of p300 histone acetyltransferase-dependent (p300-HAT-dependent) transcriptional activation. We tested this hypothesis using primary cultured rat cardiac myocytes and fibroblasts as well as two well-established mouse models of cardiac hypertrophy. Curcumin blocked phenylephrin-induced (PE-induced) cardiac hypertrophy in vitro in a dose-dependent manner. Furthermore, curcumin both prevented and reversed mouse cardiac hypertrophy induced by aortic banding (AB) and PE infusion, as assessed by heart weight/BW and lung weight/BW ratios, echocardiographic parameters, and gene expression of hypertrophic markers. Further investigation demonstrated that curcumin abrogated histone acetylation, GATA4 acetylation, and DNA-binding activity through blocking p300-HAT activity. Curcumin also blocked AB-induced inflammation and fibrosis through disrupting p300-HAT-dependent signaling pathways. Our results indicate that curcumin has the potential to protect against cardiac hypertrophy, inflammation, and fibrosis through suppression of p300-HAT activity and downstream GATA4, NF-kappaB, and TGF-beta-Smad signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Acetylation
  • Animals
  • Cardiomegaly / prevention & control*
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • DNA / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Fibrosis
  • GATA4 Transcription Factor / metabolism
  • Histone Deacetylase Inhibitors
  • Histones / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardium / pathology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / pathology
  • Rats
  • Rats, Sprague-Dawley
  • p300-CBP Transcription Factors / antagonists & inhibitors

Substances

  • Enzyme Inhibitors
  • GATA4 Transcription Factor
  • Gata4 protein, mouse
  • Histone Deacetylase Inhibitors
  • Histones
  • DNA
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Curcumin