Curcumin prevents and reverses murine cardiac hypertrophy

Hong Liang Li, Chen Liu, Geoffrey De Couto, Maral Ouzounian, Mei Sun, Ai Bing Wang, Yue Huang, Cheng Wei He, Yu Shi, Xin Chen, Mai P. Nghiem, Youan Liu, Manyin Chen, Fayez Dawood, Masahiro Fukuoka, Yuichiro Maekawa, Liyong Zhang, Andrew Leask, Asish K. Ghosh, Lorrie A. KirshenbaumPeter P. Liu

Research output: Contribution to journalArticle

108 Scopus citations

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-κB, and TGF-β-Smad signaling pathways.

Original languageEnglish (US)
Pages (from-to)879-893
Number of pages15
JournalJournal of Clinical Investigation
Volume118
Issue number3
DOIs
StatePublished - Mar 2008

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Li, H. L., Liu, C., De Couto, G., Ouzounian, M., Sun, M., Wang, A. B., Huang, Y., He, C. W., Shi, Y., Chen, X., Nghiem, M. P., Liu, Y., Chen, M., Dawood, F., Fukuoka, M., Maekawa, Y., Zhang, L., Leask, A., Ghosh, A. K., ... Liu, P. P. (2008). Curcumin prevents and reverses murine cardiac hypertrophy. Journal of Clinical Investigation, 118(3), 879-893. https://doi.org/10.1172/JCI32865