Curcumin prevents and reverses murine cardiac hypertrophy.

@article{citeulike:2481486, 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.}, address = {Division of Cardiology, Heart and Stroke/Richard Lewar Centre of Excellence, University Health Network, University of Toronto, Toronto, Ontario, Canada. Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA. Wellcome Trust Genome Campus and Sanger Institute, Hinxton, Cambridge, United Kingdom. Department of Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA. Division of Oral Biology and Department of Physiology and Pharmacology, Canadian Institutes of Health Research (CIHR) Group in Skeletal Development and Remodeling, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada. Institute of Circulatory and Respiratory Health, Canadian Institutes of Health Research, Ottawa, Ontario, Canada.}, author = {Li, Hong-Liang L. and Liu, Chen and de Couto, Geoffrey and Ouzounian, Maral and Sun, Mei and Wang, Ai-Bing B. and Huang, Yue and He, Cheng-Wei W. and Shi, Yu and Chen, Xin and Nghiem, Mai P P. and Liu, Youan and Chen, Manyin and Dawood, Fayez and Fukuoka, Masahiro and Maekawa, Yuichiro and Zhang, Liyong and Leask, Andrew and Ghosh, Asish K K. and Kirshenbaum, Lorrie A A. and Liu, Peter P P. }, citeulike-article-id = {2481486}, doi = {10.1172/JCI32865}, issn = {0021-9738}, journal = {J Clin Invest}, keywords = {cv, herb, hypertrophy}, month = {March}, number = {3}, pages = {879--893}, posted-at = {2008-03-07 03:06:51}, priority = {2}, title = {Curcumin prevents and reverses murine cardiac hypertrophy.}, url = {http://dx.doi.org/10.1172/JCI32865}, volume = {118}, year = {2008} }

TY - JOUR ID - citeulike:2481486 L3 - citeulike-article-id:2481486 TI - Curcumin prevents and reverses murine cardiac hypertrophy. JF - J Clin Invest VL - 118 IS - 3 SP - 879 EP - 893 AD - Division of Cardiology, Heart and Stroke/Richard Lewar Centre of Excellence, University Health Network, University of Toronto, Toronto, Ontario, Canada. Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA. Wellcome Trust Genome Campus and Sanger Institute, Hinxton, Cambridge, United Kingdom. Department of Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA. Division of Oral Biology and Department of Physiology and Pharmacology, Canadian Institutes of Health Research (CIHR) Group in Skeletal Development and Remodeling, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada. Institute of Circulatory and Respiratory Health, Canadian Institutes of Health Research, Ottawa, Ontario, Canada. SN - 0021-9738 N2 - 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. KW - cv KW - herb KW - hypertrophy AU - Li, Hong-Liang AU - Liu, Chen AU - de Couto, Geoffrey AU - Ouzounian, Maral AU - Sun, Mei AU - Wang, Ai-Bing AU - Huang, Yue AU - He, Cheng-Wei AU - Shi, Yu AU - Chen, Xin AU - Nghiem, Mai P AU - Liu, Youan AU - Chen, Manyin AU - Dawood, Fayez AU - Fukuoka, Masahiro AU - Maekawa, Yuichiro AU - Zhang, Liyong AU - Leask, Andrew AU - Ghosh, Asish K AU - Kirshenbaum, Lorrie A AU - Liu, Peter P PY - 2008/03/03/ UR - http://dx.doi.org/10.1172/JCI32865 ER -