Treatment with curcumin reduced acetylation levels at H3K4, H3K9, and H3K27 within GATA4 and MEF2C promoters, leading to downregulation of these genes and enhancement of cardiac performance in mice.
Does curcumin improve cardiac performance by inhibiting histone acetylation and downregulating GATA4 and MEF2C in a murine model of heart failure?
Inhibition of histone acetylation downregulates the reactivation of GATA4 and MEF2C, offering a potential epigenetic mechanism to improve cardiac performance in heart failure.
ABSTRACT The pathogenesis of heart failure involves a highly intricate process regulated by diverse epigenetic factors, transcription factors, noncoding RNAs, and cyclins. Notably, the reexpression of embryonic cardiac transcription factors, including GATA , MEF2 , and Nkx2.5 , is considered to exert critical influence in the initiation and advancement of heart failure. Nevertheless, the precise mechanisms through which epigenetic modifications drive this reprogramming of gene expression remain poorly defined. This investigation aims to clarify the role of histone acetylation in regulating the reexpression of embryonic cardiac transcription factors during heart failure. Our research indicates that during heart failure of mice, there are distinct histone acetylation modifications associated with the reexpression of these factors. Notably, GATA4 and MEF2C show significant increases, whereas Nkx2.5 shows a decrease compared to normal groups during heart failure progression. These findings imply that embryonic GATA4 and MEF2C may promote the development of heart failure, whereas Nkx2.5 does not appear to participate in disease progression. Furthermore, treatment with curcumin, a known inhibitor of histone acetylation, reduces acetylation levels at H3K4, H3K9, and H3K27 within the promoter regions of GATA4 and MEF2 C in a murine model of heart failure, leading to downregulation of these genes and subsequent enhancement of cardiac performance. In summary, our study demonstrates that p300 exerts site‐specific regulatory effects on various transcription factors via histone modifications, and low acetylation status at specific sites can inhibit reactivation of GATA4 and MEF2C during the myocardial dysfunction period thereby improving cardiac performance of mice.
Gan et al. (Fri,) conducted a other in Heart failure. Curcumin vs. Untreated heart failure mice was evaluated on Acetylation levels at H3K4, H3K9, and H3K27 within GATA4 and MEF2C promoters and cardiac performance. Treatment with curcumin reduced acetylation levels at H3K4, H3K9, and H3K27 within GATA4 and MEF2C promoters, leading to downregulation of these genes and enhancement of cardiac performance in mice.