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 (PEinduced) 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.

Cyclin-dependent Kinase-9 Is a Component of the p300/GATA4 Complex Required for Phenylephrine-induced Hypertrophy in Cardiomyocytes

“…We and others (14,15) have recently reported that a p300-specific HAT inhibitor, curcumin, can prevent the development of cardiomyocyte hypertrophy and heart failure in vivo. The present study provides evidence that Cdk9 kinase activity is required for p300 HAT activity and for the p300/GATA4 transcriptional pathway during hypertrophic responses in cardiomyocytes.…”

“…HAT activity of p300 is required for myocardial hypertrophy in vitro and for the promotion of left ventricular remodeling in vivo (13). Recently, we and others have reported that a natural p300-specific HAT inhibitor, curcumin, prevents the development of cardiomyocyte hypertrophy and heart failure in vivo, further emphasizing the importance of p300 in these processes (14,15). In addition, p300 acts as a scaffold protein in the assembly of multisubunit transcription factor complexes for specific cardiac promoters, thereby conferring further specificity.…”

Occurrence and Leave Extractable Essential Oil of Lippia multiflora M. (Verbenaceae) as Affected by Soil Acidity, Carbon, Nitrogen and Phosphorus Contents in North Cote d’Ivoire

“…The difference observed can account for genetic diversity of Lippia multiflora (Adou et al, 2011) at certain level in addition to the effect of the latitude variation (Purseglove, Brown, Green, & Robbins, 1981). However, environment effect as described by Besombes (2008) can stand out among variability factors of essential oil quality in a restricted area as much as our studied region. Soil contents of P as total and available P has shown significant influences on the concentrations of major volatile substances determined in extractable essential oils across the studied sites.…”

Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets

“…Previous studies have shown that curcumin selectively inhibits ectopic fVII synthesis by removing p300/CBP from the FVII promoter region. Furthermore, animal studies have shown that curcumin can cure cardiovascular diseases [114,115] and cancer [116] by targeting p300 activity. Therefore, anti-p300 strategies using curcumin may be clinically applicable, without posing significant toxicity.…”