Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The heart responds to stress signals by hypertrophic growth, which is accompanied by activation of the MEF2 transcription factor and reprogramming of cardiac gene expression. We show here that class II histone deacetylases (HDACs), which repress MEF2 activity, are substrates for a stress-responsive kinase specific for conserved serines that regulate MEF2-HDAC interactions. Signal-resistant HDAC mutants lacking these phosphorylation sites are refractory to hypertrophic signaling and inhibit cardiomyocyte hypertrophy. Conversely, mutant mice lacking the class II HDAC, HDAC9, are sensitized to hypertrophic signals and exhibit stress-dependent cardiomegaly. Thus, class II HDACs act as signal-responsive suppressors of the transcriptional program governing cardiac hypertrophy and heart failure.
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PMID:Class II histone deacetylases act as signal-responsive repressors of cardiac hypertrophy. 1220 37

Postnatal cardiac myocytes respond to stress signals by hypertrophic growth and activation of a fetal gene program. Recently, we showed that class II histone deacetylases (HDACs) suppress cardiac hypertrophy, and mice lacking the class II HDAC, HDAC9, are sensitized to hypertrophic signals. To further define the roles of HDACs in cardiac hypertrophy, we analyzed the effects of HDAC inhibitors on the responsiveness of primary cardiomyocytes to hypertrophic agonists. Paradoxically, HDAC inhibitors imposed a dose-dependent blockade to hypertrophy and fetal gene activation. We conclude that distinct HDACs play positive or negative roles in the control of cardiomyocyte hypertrophy. HDAC inhibitors are currently being tested in clinical trials as anti-cancer agents. Our results suggest that these inhibitors may also hold promising clinical value as therapeutics for cardiac hypertrophy and heart failure.
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PMID:Dose-dependent blockade to cardiomyocyte hypertrophy by histone deacetylase inhibitors. 1276 Dec 26

Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide. Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression. Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases. Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs. Thus, we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9, Tregs and CHF. Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients. Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA), we found that the HDAC9 mRNA expression level in NYHA grade II-III group were lower than that in NYHA grade IV group. More importantly, the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF), whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF. The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF. Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.
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PMID:Correlation between Histone Deacetylase 9 and Regulatory T Cell in Patients with Chronic Heart Failure. 3007 76

Cardiac hypertrophy is closely correlated with diverse cardiovascular diseases, augmenting the risk of heart failure and sudden death. Long non-coding RNAs (lncRNAs) have been studied in cardiac hypertrophy for their regulatory function. LncRNA MEG3 has been reported in human cancers. Whereas, it is unknown whether MEG3 regulates the growth of cardiac hypertrophy. Therefore, this study aims to investigate the specific role of MEG3 in the progression of cardiac hypertrophy. Here, we found that MEG3 contributed to the pathogenesis of cardiac hypertrophy. MEG3 expression was remarkably strengthened in the mice heart which undergone the transverse aortic constriction (TAC). Moreover, qRT-PCR analysis revealed that MEG3 was upregulated in the cardiomyocytes which were treated with Ang-II. Silenced MEG3 inhibited the increasing size of hypertrophic cardiomyocytes and reversed other hypertrophic responses. Mechanically, MEG3 could affect cardiac hypertrophy by regulating gene expression. Mechanically, we found that MEG3 could be upregulated by the transcription factor STAT3 and could regulate miR-361-5p and HDAC9 by acting as a ceRNA. Finally, rescue assays were made to do further confirmation. All our findings revealed that STAT3-inducetd upregulation of lncRNA MEG3 controls cardiac hypertrophy by regulating miR-362-5p/HDAC9 axis.
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PMID:STAT3-induced upregulation of lncRNA MEG3 regulates the growth of cardiac hypertrophy through miR-361-5p/HDAC9 axis. 3067 21

The complex pathobiology underlying cardiovascular diseases (CVDs) has yet to be explained. Aberrant epigenetic changes may result from alterations in enzymatic activities, which are responsible for putting in and/or out the covalent groups, altering the epigenome and then modulating gene expression. The identification of novel individual epigenetic-sensitive trajectories at single cell level might provide additional opportunities to establish predictive, diagnostic and prognostic biomarkers as well as drug targets in CVDs. To date, most of studies investigated DNA methylation mechanism and miRNA regulation as epigenetics marks. During atherogenesis, big epigenetic changes in DNA methylation and different ncRNAs, such as miR-93, miR-340, miR-433, miR-765, CHROME, were identified into endothelial cells, smooth muscle cells, and macrophages. During man development, lipid metabolism, inflammation and homocysteine homeostasis, alter vascular transcriptional mechanism of fundamental genes such as ABCA1, SREBP2, NOS, HIF1. At histone level, increased HDAC9 was associated with matrix metalloproteinase 1 (MMP1) and MMP2 expression in pro-inflammatory macrophages of human carotid plaque other than to have a positive effect on toll like receptor signaling and innate immunity. HDAC9 deficiency promoted inflammation resolution and reverse cholesterol transport, which might block atherosclerosis progression and promote lesion regression. Here, we describe main human epigenetic mechanisms involved in atherosclerosis, coronary heart disease, ischemic stroke, peripheral artery disease; cardiomyopathy and heart failure. Different epigenetics mechanisms are activated, such as regulation by circular RNAs, as MICRA, and epitranscriptomics at RNA level. Moreover, in order to open new frontiers for precision medicine and personalized therapy, we offer a panoramic view on the most innovative bioinformatic tools designed to identify putative genes and molecular networks underlying CVDs in man.
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PMID:Epigenetic-sensitive pathways in personalized therapy of major cardiovascular diseases. 3210 74

Class IIa histone deacetylases (HDACs) repress cardiomyocyte hypertrophy through association with the prohypertrophic transcription factor (TF) myocyte enhancer factor-2 (MEF2). The four class IIa HDACs - HDAC4, -5, -7, and -9 - are subject to signal-dependent phosphorylation by members of the Ca2+/calmodulin-dependent protein kinase (CaMK) group. In response to stress, HDAC4, HDAC5, and HDAC9 undergo phosphorylation-induced nuclear export in cardiomyocytes, freeing MEF2 to stimulate progrowth genes; it was generally assumed that HDAC7 is also antihypertrophic. However, in this issue of the JCI, Hsu and colleagues demonstrate that, in sharp contrast to the other class IIa HDACs, HDAC7 is constitutively localized to the cardiomyocyte cytoplasm, where it promotes cardiac hypertrophy. Phosphorylation of HDAC7 by the CaMK group member salt-inducible kinase 1 (SIK1) stabilized the deacetylase, leading to increased expression of c-Myc, which in turn stimulated a pathological gene program. These unexpected findings highlight the SIK1/HDAC7 signaling axis as a promising target for the treatment of cardiac hypertrophy and heart failure.
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PMID:The black sheep of class IIa: HDAC7 SIKens the heart. 3236 32