The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Pharmacology

Background:

• Hemodynamic overload causes maladaptive cardiomyocyte hypertrophy.
• Nuclear acetylation, regulated by histone deacetylases and p300 (a histone acetyltransferase - HAT), is a key signaling event.
• Curcumin, a polyphenol from turmeric, inhibits HAT activity, specifically targeting p300/CREB-binding protein.

Purpose of the Study:

• To investigate curcumin's effect on GATA4 acetylation and DNA binding in cardiomyocytes.
• To determine if curcumin disrupts the p300/GATA4 complex and represses hypertrophic responses.
• To evaluate curcumin's efficacy in preventing cardiac dysfunction in vivo heart failure models.

Main Methods:

• Experiments were conducted on rat cardiomyocytes and in vivo rat models of heart failure (hypertensive heart disease and myocardial infarction).
• Assessed curcumin's impact on hypertrophy-induced GATA4 acetylation and DNA-binding abilities.
• Analyzed the p300/GATA4 complex formation and its role in hypertrophic responses.
• Evaluated cardiac function, myocardial wall thickness, and diameter in response to curcumin treatment.

Main Results:

• Curcumin inhibited hypertrophy-induced GATA4 acetylation and DNA binding in rat cardiomyocytes.
• Curcumin disrupted the p300/GATA4 complex, repressing agonist- and p300-induced hypertrophic responses.
• In vivo, curcumin prevented the deterioration of systolic function and reduced cardiac remodeling in two distinct heart failure models.

Conclusions:

• Inhibition of p300 HAT activity by curcumin represents a potential therapeutic strategy for heart failure.
• Curcumin's ability to modulate GATA4 acetylation and p300 complex formation is crucial for its cardioprotective effects.
• The nontoxic dietary compound curcumin may offer a novel approach for treating human heart failure.