title: Curcumin prevents and reverses murine cardiac hypertrophy.
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.
authors.affiliation: Division of Cardiology, Heart and Stroke/Richard Lewar Centre of Excellence, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Geoffrey
authors.initials: G
authors.lastname: de Couto
authors.forename: Maral
authors.initials: M
authors.lastname: Ouzounian
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.forename: Ai-Bing
authors.initials: AB
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: He
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Mai P
authors.initials: MP
authors.lastname: Nghiem
authors.forename: Youan
authors.initials: Y
authors.lastname: Liu
authors.forename: Manyin
authors.initials: M
authors.lastname: Chen
authors.forename: Fayez
authors.initials: F
authors.lastname: Dawood
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Liyong
authors.initials: L
authors.lastname: Zhang
authors.forename: Andrew
authors.initials: A
authors.lastname: Leask
authors.forename: Asish K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Lorrie A
authors.initials: LA
authors.lastname: Kirshenbaum
authors.forename: Peter P
authors.initials: PP
authors.lastname: Liu
mesh_terms: D000107:Acetylation; D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control*; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005355:Fibrosis; D050991:GATA4 Transcription Factor / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors; D000099224:p300-CBP-Associated Factor
chemical_list: D003474:Curcumin; D004247:DNA; D004791:Enzyme Inhibitors; D050991:GATA4 Transcription Factor; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C484171:Gata4 protein, mouse