Curcumin prevents and reverses murine cardiac hypertrophy (J Clin Invest, 2008, 119:879-893)

報告日期: 2008/11/25
報告時間: 17:05/17:55
報告學生: 張程翔
講評老師: 謝清河
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971125-3.pdf

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. Kirshenbaum, and Peter P. Liu

J. Clin. Invest. 118:879–893 (2008)

 

Student: 張程翔

Commentator: 謝清河 老師

Time: 2008/11/25/17:05~17:55

Place: 602

 

Abstract

Chromatin remodeling is one of the key control points for gene regulation in the cardiac hypertrophy. Relaxation of chromatin, mediated by p300-HAT (histone acetyltransferase), has been known to induce cardiac hypertrophy, suggesting p300-HAT as a potential target to treat cardiac hypertrophy and subsequent heart failure. Recently, a natural polyphenolic compound, curcumin, has been shown to be an inhibitor of p300-HAT. However, the effect of curcumin on the treatment of cardiac hypertrophy has not been documented. In this paper, the authors hypothesized that curcumin attenuates cardiac hypertrophy by impairing p300-HAT activity. Phenylephrin (PE) and aortic banding (AB) were used to induce cardiac hypertrophy in this study. The authors demonstrated that pretreatment with curcumin inhibits PE-induced cardiac hypertrophy in vitro and in vivo. The protection of curcumin was also found in AB-induced cardiac hypertrophy in vivo. Molecular analysis found that curcumin abrogates histone acetylation, GATA4 acetylation and DNA-binding activity through blocking p300-HAT activity. In addition, curcumin blocked AB-induced inflammation and fibrosis through disrupting p300-HAT–dependent signaling pathways. Importantly, the authors showed that curcumin not only prevents cardiac hypertrophy, but also ameliorates established cardiac hypertrophy. Taken together, these findings support the concept of curcumin as a preventive and therapeutic candidate against cardiac hypertrophy and heart failure.