Regulation of Gene Expression in the Failing Myocardium: Evidence for a Heart Failure Gene Program

1994 ◽  
pp. 7-16
Author(s):  
Arthur M. Feldman ◽  
Vinnette T. Edwards ◽  
Jennifer E. Lawrence ◽  
Randall E. Williams ◽  
Warren D. Rosenblum
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Regulation Of Gene Expression

scholarly journals Food Bioactive HDAC Inhibitors in the Epigenetic Regulation of Heart Failure

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1120 ◽  
Author(s):  
Levi Evans ◽  
Bradley Ferguson
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Histone Deacetylases ◽  
Regulation Of Gene Expression ◽  
Hdac Inhibitors ◽  
Drug Efficacy ◽  
Histone Deacetylation ◽  
Epigenetic Modifiers

Approximately 5.7 million U.S. adults have been diagnosed with heart failure (HF). More concerning is that one in nine U.S. deaths included HF as a contributing cause. Current HF drugs (e.g., β-blockers, ACEi) target intracellular signaling cascades downstream of cell surface receptors to prevent cardiac pump dysfunction. However, these drugs fail to target other redundant intracellular signaling pathways and, therefore, limit drug efficacy. As such, it has been postulated that compounds designed to target shared downstream mediators of these signaling pathways would be more efficacious for the treatment of HF. Histone deacetylation has been linked as a key pathogenetic element for the development of HF. Lysine residues undergo diverse and reversible post-translational modifications that include acetylation and have historically been studied as epigenetic modifiers of histone tails within chromatin that provide an important mechanism for regulating gene expression. Of recent, bioactive compounds within our diet have been linked to the regulation of gene expression, in part, through regulation of the epi-genome. It has been reported that food bioactives regulate histone acetylation via direct regulation of writer (histone acetyl transferases, HATs) and eraser (histone deacetylases, HDACs) proteins. Therefore, bioactive food compounds offer unique therapeutic strategies as epigenetic modifiers of heart failure. This review will highlight food bio-actives as modifiers of histone deacetylase activity in the heart.

Abstract 12596: Manipulation of Gut Microbiota Influences Myocardial Mass in Mice

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Takehiro Kamo
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Body Weight ◽  
Gut Microbiota ◽  
Expression Profiles ◽  
Oral Treatment ◽  
Regulation Of Gene Expression ◽  
Heart Weight ◽  
Myocardial Mass ◽  
Antibiotic Cocktail

Introduction: Gut microbiota have developed a close relationship with human host during the co-evolutionary process for millions of years, and they play an essential role in the maintenance of host homeostasis. There is accumulating evidence that an imbalance in the gut microbial communities, referred to as dysbiosis, is associated with human pathologies including cardiovascular diseases. We and others have recently demonstrated that heart failure is associated with gut microbiota dysbiosis using 16S ribosomal RNA gene sequencing of fecal samples from patients with heart failure. This finding suggests a potential significance of gut microbiota in the pathophysiology of heart failure. However, the link between the gut microbiota and the heart remains largely unclear. Hypothesis: We hypothesized that manipulation of gut microbiota influences the structure of the heart. Methods: To determine the effects of gut microbiota depletion, cardiac structure and gene expression were evaluated in mice following treatment with orally administered broad-spectrum antibiotic cocktail. We subsequently explored the effects of administration of a single antibiotic agent on myocardial structure. Results: Antibiotic cocktail-treated mice showed a remarkable decrease in myocardial mass and cardiomyocyte size as compared with untreated mice (mean [±SD] ratio of heart weight to body weight, 3.87±0.25 mg/g in 44 antibiotic-treated mice vs. 4.38±0.21 mg/g in 45 untreated mice). The decrease in myocardial mass was associated with substantial changes in gene expression profiles in the heart, including the expression of genes encoding sarcomere proteins and extracellular matrix proteins. In addition, oral treatment with ampicillin alone led to a significant decrease in myocardial mass (mean [±SD] ratio of heart weight to body weight, 3.52±0.24 mg/g in 11 ampicillin-treated mice vs. 4.10±0.24 mg/g in 12 untreated mice). Conclusions: These results suggest that gut microbiota may modulate myocardial mass through the remote regulation of gene expression in the heart. Our study indicates an intimate relationship between the gut microbiota and the heart, and suggests the potential efficacy of manipulating gut microbiota in the prevention and treatment of heart failure.

scholarly journals Dysregulated micro-RNAs and long noncoding RNAs in cardiac development and pediatric heart failure

2020 ◽  
Vol 318 (5) ◽  
pp. H1308-H1315 ◽  
Author(s):  
Lee Toni ◽  
Frehiwet Hailu ◽  
Carmen C. Sucharov
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Cardiac Development ◽  
Heart Diseases ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Cardiovascular Development ◽  
Micro Rnas

Noncoding RNAs (ncRNAs) are broadly described as RNA molecules that are not translated into protein. The investigation of dysregulated ncRNAs in human diseases such as cancer, neurological, and cardiovascular diseases has been under way for well over a decade. Micro-RNAs and long noncoding RNAs (lncRNAs) are the best characterized ncRNAs. These ncRNAs can have profound effects on the regulation of gene expression during cardiac development and disease. Importantly, ncRNAs are significant regulators of gene expression in several congenital heart diseases and can positively or negatively impact cardiovascular development. In this review, we focus on literature involving micro-RNAs and lncRNAs in the context of pediatric cardiovascular diseases, preclinical models of heart failure, and cardiac development.

Abstract 375: Insights Into Molecular Mechanism of Cardiovascular Disorder in HIV+ Patients

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Manish Gupta ◽  
Kaylyn Scanlon ◽  
Avni Mukker ◽  
Deepti Gupta ◽  
Jay Rappaport ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Drug Treatment ◽  
Regulation Of Gene Expression ◽  
Cardiovascular Disorder ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Pcr Array ◽  
Hiv Patients ◽  
Antiretroviral Drug

Background: Antiretroviral therapy (ART) improves the survival of people living with HIV (PLHIV); however, the rate of cardiovascular disorder and heart failure is significantly increased among the PLHIV. Molecular basis of heart failure in the PLHIV undergoing antiretroviral drug treatment is not clear. The aim of this study is to explore the role of antiretroviral drugs in post translational modification of histones and its epigenetic regulation of gene expression in cardiomyocytes. Methods and Results: Primary rat ventricular cardiomyocytes were treated with a combination of antiretroviral drugs (5 μM of Atazanavir, Abacavir, Ritonavir and Lamivudine) for 4, 12 and 24 hours, and expression of major histone marks playing a role in gene activation (H3K9ac and H3K27ac) and repression (H3K27me3, H3K9me3) were evaluated by western blotting. Our data suggest that treatment with antiretroviral drugs leads to de-acetylation at H3K9ac and H3K27ac, and promotes methylation at H3K27me3 and H3k9me3. Additionally, the expression of epigenetic modifying enzymes was examined by PCR array in cardiomyocytes treated with antiretroviral drugs. PCR array data show that histone deacetylase enzyme Sirt1/2, and methyltransferase enzyme Suv39h1 and Ezh12 were upregulated in drug treated cardiomyocytes. Further, western blot data show that Sirt1, Suv39h1 and Ezh2 protein expression was significantly upregulated in drugs treated cardiomyocytes. Moreover, expression analysis of human cardiac tissue further shows that expression of Sirt1, Suv39h1 and Ezh2 was significantly upregulated in HIV+ patients heart compares to healthy donor. Mechanistically, our data show that expression of epigenetic modifying enzymes was differentially regulated in drug treated cardiomyocytes which may lead to epigenetic modifications of histone proteins. Conclusion: Antiretroviral drug treatment promotes epigenetic alteration in the chromatin which may lead to a change in gene expression of cardiomyocytes. This study may lead to novel therapeutic strategies for the treatment of heart failure in PLWHA.

scholarly journals Regulatory RNAs in Heart Failure

Circulation ◽  
2020 ◽  
Vol 141 (4) ◽  
pp. 313-328 ◽  
Author(s):  
Clarissa Pedrosa da Costa Gomes ◽  
Blanche Schroen ◽  
Gabriela M. Kuster ◽  
Emma L. Robinson ◽  
Kerrie Ford ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Noncoding Rna ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Circular Rnas ◽  
Regulatory Rna ◽  
Messenger Rnas ◽  
Protein Coding

Cardiovascular disease is an enormous socioeconomic burden worldwide and remains a leading cause of mortality and disability despite significant efforts to improve treatments and personalize healthcare. Heart failure is the main manifestation of cardiovascular disease and has reached epidemic proportions. Heart failure follows a loss of cardiac homeostasis, which relies on a tight regulation of gene expression. This regulation is under the control of multiple types of RNA molecules, some encoding proteins (the so-called messenger RNAs) and others lacking protein-coding potential, named noncoding RNAs. In this review article, we aim to revisit the notion of regulatory RNA, which has been thus far mainly confined to noncoding RNA. Regulatory RNA, which we propose to abbreviate as regRNA, can include both protein-coding RNAs and noncoding RNAs, as long as they contribute, directly or indirectly, to the regulation of gene expression. We will address the regulation and functional role of messenger RNAs, microRNAs, long noncoding RNAs, and circular RNAs (ie, regRNAs) in heart failure. We will debate the utility of regRNAs to diagnose, prognosticate, and treat heart failure, and we will provide directions for future work.

Linking transcription, RNA polymerase II elongation and alternative splicing

2020 ◽  
Vol 477 (16) ◽  
pp. 3091-3104 ◽  
Author(s):  
Luciana E. Giono ◽  
Alberto R. Kornblihtt
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Rna Polymerase Ii ◽  
Environmental Changes ◽  
Transcription Elongation ◽  
Single Gene ◽  
Regulation Of Gene Expression ◽  
Regulation Of Transcription ◽  
Stepping Stones ◽  
Eukaryotic Transcription

Gene expression is an intricately regulated process that is at the basis of cell differentiation, the maintenance of cell identity and the cellular responses to environmental changes. Alternative splicing, the process by which multiple functionally distinct transcripts are generated from a single gene, is one of the main mechanisms that contribute to expand the coding capacity of genomes and help explain the level of complexity achieved by higher organisms. Eukaryotic transcription is subject to multiple layers of regulation both intrinsic — such as promoter structure — and dynamic, allowing the cell to respond to internal and external signals. Similarly, alternative splicing choices are affected by all of these aspects, mainly through the regulation of transcription elongation, making it a regulatory knob on a par with the regulation of gene expression levels. This review aims to recapitulate some of the history and stepping-stones that led to the paradigms held today about transcription and splicing regulation, with major focus on transcription elongation and its effect on alternative splicing.

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