[HTML][HTML] Curcumin prevents and reverses murine cardiac hypertrophy

HL Li, C Liu, G De Couto, M Ouzounian… - The Journal of …, 2008 - Am Soc Clin Investig
HL Li, C Liu, G De Couto, M Ouzounian, M Sun, AB Wang, Y Huang, CW He, Y Shi, X Chen…
The Journal of clinical investigation, 2008Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation