Histone Acetylation Domains Are Differentially Induced during Development of Heart Failure in Dahl Salt-Sensitive Rats

Abstract

Histone acetylation by epigenetic regulators has been shown to activate the transcription of hypertrophic response genes, which subsequently leads to the development and progression of heart failure. However, nothing is known about the acetylation of the histone tail and globular domains in left ventricular hypertrophy or in heart failure. The acetylation of H3K9 on the promoter of the hypertrophic response gene was significantly increased in the left ventricular hypertrophy stage, whereas the acetylation of H3K122 did not increase in the left ventricular hypertrophy stage but did significantly increase in the heart failure stage. Interestingly, the interaction between the chromatin remodeling factor BRG1 and p300 was significantly increased in the heart failure stage, but not in the left ventricular hypertrophy stage. This study demonstrates that stage-specific acetylation of the histone tail and globular domains occurs during the development and progression of heart failure, providing novel insights into the epigenetic regulatory mechanism governing transcriptional activity in these processes.

Pyrazole-Curcumin Suppresses Cardiomyocyte Hypertrophy by Disrupting the CDK9/CyclinT1 Complex

“…The 1-2-day-old Sprague Dawley rats used in the study were purchased from Japan SLC Inc. (Shizuoka, Japan). Primary cardiomyocytes were isolated from neonatal Sprague-Dawley rats as described previously [26]. Briefly, isolated cardiomyocytes were cultured in Dulbecco's Modified Eagle Medium (DMEM; L1N7624) (Sigma-Aldrich, St. Louis, MO, USA) containing 10% fetal bovine serum (Sigma-Aldrich) and stabilized penicillin/streptomycin solution (Nacalai Tesque, Kyoto, Japan) at 37 • C for 48 h. CUR, PPC, or PyrC were added to cardiomyocytes.…”

Chrysanthemum morifolium Extract Ameliorates Doxorubicin-Induced Cardiotoxicity by Decreasing Apoptosis

“…Echocardiography was performed using a 10-12 MHz probe and a Sonos 5500 Ultrasound System (Philips, Amsterdam, The Netherlands) as described previously [27,32,33]. Left ventricular internal diameter end-diastole (LVIDd), left ventricular internal diameter end-systole (LVIDs), and left ventricular posterior wall thickness (LVPWT) were obtained from M-mode recordings.…”

Acetyltransferase p300 Is a Putative Epidrug Target for Amelioration of Cellular Aging-Related Cardiovascular Disease

“…These results further indicate the significant contribution of acetyltransferase p300 in cardiac hypertrophy and heart failure [ 44 ]. Interestingly, a recent study showed that while the levels of Ac-H3K9 on ANP, BNP, and β-MHC promoters are significantly increased during left ventricular hypertrophy stage in Dahl salt-sensitive rats after 6 weeks salt exposure, the levels of Ac-H3K122 on ANP, BNP and β-MHC promoters are elevated at heart failure stage after 15 weeks salt exposure compared to age matched salt-resistant rats [ 45 ]. These results clearly established the stage specific recruitment of acetyltransferase p300 to target genes and lysine acetylation of specific histones to target gene promoters play critical role in progression of cardiac pathologies.…”

“…These results clearly established the stage specific recruitment of acetyltransferase p300 to target genes and lysine acetylation of specific histones to target gene promoters play critical role in progression of cardiac pathologies. Authors further delineated the underlying mechanism of stage-specific recruitment of p300 to hypertrophy responsive gene promoters and showed that the interaction of acetyltransferase p300 with BRG1, a functional subunit of chromatin remodeling complex, and their recruitments to target genes are increased in late heart failure stage but not in early left ventricular hypertrophy stage [ 45 ]. Together, these results indicate that p300-mediated epigenetic regulation of genes involved in hypertrophy and eventual heart failure are progressive and disease stage-specific.…”

“…Thus, inhibition of acetyltransferase activity normalize hypertrophic gene expression including ANP, BNP, Cx43, cTnT, and β-MHC and mitigate murine hypertrophic cardiomyopathy [ 48 ]. A recent study demonstrates that while overexpression of p300 in neonatal rat cardiomyocytes leads to increased acetylation of H3K9 and H3K122 and increased expression of ANP, BNP, and β-MHC, siRNA-mediated depletion of p300 in cardiomyocytes blunts PE-induced acetylation of H3K9 and H3K122, and the expression of PE-induced hypertrophy responsive genes [ 45 ]. These findings further signify the key role of acetyltransferase p300 in specific histone lysine acetylation and PE-induced pathological cardiac hypertrophy.…”