Curcumin prevents and reverses murine cardiac hypertrophy
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Post-publication record
- Nature
- Retraction
- Reason
- Duplication of/in Image;Error in Analyses;
- Date
- 7/1/2009 0:00
- Flagged by OpenAlex?
- Yes
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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.
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The record
- Venue
- Journal of Clinical Investigation
- Topic
- Curcumin's Biomedical Applications
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- University of ManitobaWestern UniversitySt. Boniface HospitalCanadian Institutes of Health ResearchHeart and Stroke FoundationToronto General HospitalUniversity of TorontoUniversity Health Network
- Funders
- Institute of Circulatory and Respiratory HealthCanadian Institutes of Health ResearchUniversity of TorontoUniversity of ManitobaHeart and Stroke Foundation of Canada
- Keywords
- CurcuminCardiac fibrosisMuscle hypertrophyFibrosisAcetylationHistoneP300-CBP Transcription FactorsChromatin remodelingBiologyEndocrinologyCancer researchInternal medicineChemistryPharmacologyMedicineHistone AcetyltransferasesBiochemistryGene
- Has abstract in OpenAlex
- yes