The impact of epigenetics on cardiovascular disease

2020 ◽  
Vol 98 (1) ◽  
pp. 12-22 ◽  
Author(s):  
Dimple Prasher ◽  
Steven C. Greenway ◽  
Raja B. Singh
Keyword(s):  
Cardiac Fibrosis ◽  
Mortality And Morbidity ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Novel Biomarkers ◽  
External Risk ◽  
And Function ◽  
The Impact

Mortality and morbidity from cardiovascular diseases (CVDs) represents a huge burden to society. It is recognized that environmental factors and individual lifestyles play important roles in disease susceptibility, but the link between these external risk factors and our genetics has been unclear. However, the discovery of sequence-independent heritable DNA changes (epigenetics) have helped us to explain the link between genes and the environment. Multiple diverse epigenetic processes, including DNA methylation, histone modification, and the expression of non-coding RNA molecules affect the expression of genes that produce important changes in cellular differentiation and function, influencing the health and adaptability of the organism. CVDs such as congenital heart disease, cardiomyopathy, heart failure, cardiac fibrosis, hypertension, and atherosclerosis are now being viewed as much more complex and dynamic disorders. The role of epigenetics in these and other CVDs is currently under intense scrutiny, and we can expect important insights to emerge, including novel biomarkers and new approaches to enable precision medicine. This review summarizes the recent advances in our understanding of the role of epigenetics in CVD.

scholarly journals The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 902
Author(s):  
Eva Costanzi ◽  
Carolina Simioni ◽  
Gabriele Varano ◽  
Cinzia Brenna ◽  
Ilaria Conti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Vesicles ◽  
Tumor Metastasis ◽  
Biological Processes ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Donor Cells ◽  
Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

scholarly journals Long Non-Coding RNA 554 Promotes Cardiac Fibrosis via TGF-β1 Pathway in Mice Following Myocardial Infarction

2020 ◽  
Vol 11 ◽  
Author(s):  
Bihui Luo ◽  
Zhiyu He ◽  
Shijun Huang ◽  
Jinping Wang ◽  
Dunzheng Han ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Non Coding Rna ◽  
Novel Target ◽  
And Function ◽  
Tgf Β1

Rationale: Cardiac fibrosis is observed in nearly every form of myocardial disease. Long non-coding RNAs (lncRNAs) have been shown to play an important role in cardiac fibrosis, but the detailed molecular mechanism remains unknown.Object: We aimed at characterizing lncRNA 554 expression in murine cardiac fibroblasts (CFs) after myocardial infarction (MI) to identify CF-enriched lncRNA and investigate its function and contribution to cardiac fibrosis and function.Methods and Results: In this study, we identified lncRNA NONMMUT022554 (lncRNA 554) as a regulator of MI-induced cardiac fibrosis. We found that lncRNA 554 was significantly up-regulated in the mouse hearts following MI. Further study showed that lncRNA 554 was predominantly expressed in cardiac fibroblasts, indicating a potential role of lncRNA 554 in cardiac fibrosis. In vitro knockdown of lncRNA 554 by siRNA suppressed fibroblasts migration and expression of extracellular matrix (ECM); while overexpression of lncRNA 554 promoted expression of ECM genes. Consistently, lentivirus mediated in vivo knockdown of lncRNA 554 could inhibit cardiac fibrosis and improve cardiac function in mouse model of MI. More importantly, TGF-β1 inhibitor (TEW-7197) could reverse the pro-fibrotic function of lncRNA 554 in CFs. This suggests that the effects of lncRNA 554 on cardiac fibrosis is TGF-β1 dependent.Conclusion: Collectively, our study illustrated the role of lncRNA 554 in cardiac fibrosis, suggested that lncRNA 554 might be a novel target for cardiac fibrosis.

Role of microRNAs in Hepatic Stellate Cells and Hepatic Fibrosis: an Update

2020 ◽  
Vol 26 ◽  
Author(s):  
Sai Zhu ◽  
Xin Chen ◽  
Yu Chen ◽  
Xiao-Feng Li ◽  
Si-Yu Chen ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Pathological Process ◽  
Untranslated Regions ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Major Cell Type ◽  
Novel Biomarkers

: MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate the expression of targets genes by binding to the 3′-untranslated regions. They play vital roles in diverse biological processes, including the development of hepatic fibrosis (HF). HF is characterized by the accumulation of extracellular matrix (ECM) and hepatic stellate cells (HSCs) are considered a major cell type for producing ECM. Alteration of the HSC phenotype plays a crucial role in the HF pathological process. miRNAs involved in various biological process, such as differentiation, apoptosis, migration, and their relevant signaling pathways, are expressed in HSCs; however, emerging evidence indicates that numerous miRNAs are abnormally expressed in activated HSCs. In this review, we summarize the categorization of miRNAs in HF and describe the relationships among them. We also discuss miRNAs recently discovered to be related to HF, and attempt to find potential miRNAs that may serve as novel biomarkers for use in HF treatment.

scholarly journals HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling

2019 ◽  
Author(s):  
Han Hu ◽  
Mingyang Jiang ◽  
Yangpo Cao ◽  
Zhuojun Zhang ◽  
Bin Jiang ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Rna Binding ◽  
Myocardial Hypertrophy ◽  
Cardiac Remodelling ◽  
Mouse Heart ◽  
Regulatory Processes ◽  
Elevated Expression ◽  
And Function ◽  
The Impact

Abstract Aims The elevated expression of phospholamban (PLB) has been observed in heart failure and cardiac remodelling, inhibiting the affinity of Ca2+ pump to Ca2+ thereby impairing heart relaxation. However, the mechanisms underlying the regulation of PLB remains to be further studied. The present study aims to test the role of RNA-binding protein HuR in the regulation of PLB and the impact of this regulatory process in cardiac remodelling. Methods and results A mouse model specifically deleted HuR in cardiomyocytes were used for testing the role of HuR in regulating PLB during isoproterenol (ISO)-induced cardiac remodelling. HuR deficiency did not significantly influence the phenotype and function of mouse heart under static status. However, deletion of HuR in cardiomyocytes mitigated the effect of ISO in inducing PLB expression and reducing β1-AR expression, in turn aggravating ISO-induced myocardial hypertrophy and cardiac fibrosis. In H9C2 cells, association of HuR with PLB and β1-AR mRNAs stabilized PLB mRNA and destabilized β1-AR mRNA, respectively. Conclusion HuR stabilizes PLB mRNA and destabilizes β1-AR mRNA. The HuR-PLB and HuR-β1-AR regulatory processes impact on ISO-induced cardiac remodelling.

scholarly journals The Role of MiR-124 in Bladder Cancer – A Review of the Literature

2021 ◽  
Vol 29 (1) ◽  
pp. 9-18
Author(s):  
Costin Petcu ◽  
Catalin Baston ◽  
Emil Angelescu ◽  
Maria Mirela Iacob ◽  
Ileana Constantinescu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cellular Functions ◽  
Rna Molecules ◽  
Diagnosis And Prognosis ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Normal Urothelium

Abstract MicroRNAs (miRNAs) are a group of non-coding RNA molecules that have an important role in modulating the expression of genes involved in regulating cellular functions. A growing number of studies suggest the abnormal expression of microRNAs in different types of cancer cells. MiRNA-124 is a microRNA that is down-regulated in many types of cancer cells, including bladder cancer. Our objective is to provide a review of the key publications that studied the effect of miR-124 on bladder cancer. This review focus on the targets and different pathways of miR-124 that were identified in various studies and differences between their expressions in normal urothelium and tumor tissues. We also include data regarding urinary methylations levels of miR-124 and their role in bladder cancer diagnosis and prognosis. Subsequently, we establish future perspectives of miR-124 research and its promising role in bladder cancer.

scholarly journals Identification of the conserved long non-coding RNAs in myogenesis

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anupam Bhattacharya ◽  
Simang Champramary ◽  
Tanya Tripathi ◽  
Debajit Thakur ◽  
Ilya Ioshikhes ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Muscle Development ◽  
Three Dimensional ◽  
C2c12 Cells ◽  
Mouse Muscle ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Novel Approach ◽  
Non Coding Rna ◽  
Topologically Associated Domains

Abstract Background Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). However, the function of lncRNAs in gene regulation is not well understood; moreover, finding conserved lncRNA across species is a challenging task. Therefore, we propose a novel approach to identify conserved lncRNAs and functionally annotate these molecules. Results In this study, we exploited existing myogenic transcriptome data and identified conserved lncRNAs in mice and humans. We identified the lncRNAs expressing differentially between the early and later stages of muscle development. Differential expression of these lncRNAs was confirmed experimentally in cultured mouse muscle C2C12 cells. We utilized the three-dimensional architecture of the genome and identified topologically associated domains for these lncRNAs. Additionally, we correlated the expression of genes in domains for functional annotation of these trans-lncRNAs in myogenesis. Using this approach, we identified conserved lncRNAs in myogenesis and functionally annotated them. Conclusions With this novel approach, we identified the conserved lncRNAs in myogenesis in humans and mice and functionally annotated them. The method identified a large number of lncRNAs are involved in myogenesis. Further studies are required to investigate the reason for the conservation of the lncRNAs in human and mouse while their sequences are dissimilar. Our approach can be used to identify novel lncRNAs conserved in different species and functionally annotated them.

Abstract MP259: The Role Of Sertad4 In Pathological Cardiac Remodeling

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Matthew Stratton ◽  
Ashley Francois ◽  
Oscar Bermeo-Blanco ◽  
Alessandro Canella ◽  
Lynn Marcho ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Systolic Function ◽  
Myocardial Infarct ◽  
Proteasome Inhibition ◽  
Rna Seq ◽  
Expression Of Genes ◽  
M Phase ◽  
Tgf Β1

Over 6 million Americans suffer from heart failure (HF) while the 5-year mortality rate following first admission for HF is over 40%. Cardiac fibrosis is a clinical hallmark of HF, regardless of the initiating pathology and is thought to contribute to disease progression. Using an epigenomics discovery approach, we uncovered a nuclear protein, Sertad4, as a potential anti-fibrotic target. Our data indicate that Sertad4 is a positive regulator of fibroblast activation. Specifically, cultured cardiac fibroblast experiments demonstrate that Sertad4 targeting with shRNAs blocks fibroblast proliferation and causes cells to arrest in the G2/M phase of the cell cycle. Also, shRNA targeting of Sertad4 dramatically blocked activation of myofibroblast differentiation genes (αSMA/POSTN/COL1A1). Mechanistically, these effects appear to be mediated by Sertad4 regulation of SMAD2 protein stability in the presence of TGF-β1 stimulation as demonstrated by proteasome inhibition experiments. RNA-seq analysis indicate that Sertad4 also regulates the expression of genes involved in ubiquitination and proteasome degradation. Next, we sought to determine the effect of global Sertad4 knockout on post-myocardial infarct (MI) remodeling and cardiac function in mice. After 4 weeks of permanent LAD ligation, echocardiography was performed to measure systolic function. Relative to wild-type (WT) controls, the Sertad4 KO mice showed preserved systolic function as evident by improved ejection fraction (WT 14.4 +/- 3.6 vs. KO 33.9+/-5.9, p=0.035) and fractional shortening (WT 6.5 +/- 1.7 vs. KO 16.4 +/- 3.4, p=0.046). β-gal staining in the Sertad4/LacZ reporter mouse subjected to MI showed robust Sertad4/LacZ expression in the ischemic scar and boarder-zone with almost no expression in control hearts. This data supports the notion that Sertad4 has a key role in cardiac remodeling in response to ischemic injury.

Abstract 445: A Pro-Fibrotic Role of Interleukin-4 in Cardiac Remodeling and Dysfunction

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Hongmei Peng ◽  
Oscar Carretero ◽  
Xiao-Ping Yang ◽  
Pablo Nakagawa ◽  
Jiang Xu ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Interleukin 4 ◽  
Ang Ii ◽  
Collagen Production ◽  
And Function ◽  
First Time ◽  
Mini Pump

Elevated interleukin-4 (IL-4) levels are positively related to cardiac fibrosis in heart failure and hypertension. Using Balb/c exhibiting high circulating IL-4, Balb/c- Il4 tm2Nnt (IL-4 knockout with Balb/c background, IL-4 -/- ) and C57BL/6 mice, as well as cultured cardiac fibroblasts (CFs), we hypothesized that 1) high levels of IL-4 result in cardiac fibrosis, making the heart susceptible to angiotensin II (Ang II)-induced damage, and 2) IL-4 potently stimulates collagen production by CFs. Each strain (9- to 12-week old male) received vehicle or Ang II (1.4 mg/kg/day, s.c. via osmotic mini-pump) for 8 weeks. Cardiac fibrosis and function were determined by histology and echocardiography, respectively. Compared to C57BL/6, Balb/c mice had doubled interstitial collagen in the heart, enlarged left ventricle and decreased cardiac function along with elevated cardiac IL-4 protein (1.00±0.08 in C57BL/6 vs 2.61±0.46 in Balb/c, p <0.05); all those changes were significantly attenuated in IL-4 -/- (Table 1). Ang II further deteriorated cardiac fibrosis and dysfunction in Balb/c; these detrimental effects were attenuated in IL-4 -/- , although the three strains had a similar level of hypertension. In vitro study revealed that IL-4Rα was constitutively expressed in CFs (Western blot), and IL-4 potently stimulated collagen production by CFs (hydroxproline assay, from 18.89±0.85 to 38.81±3.61 μg/mg at 10 ng/ml, p <0.01). Our study demonstrates for the first time that IL-4, as a potent pro-fibrotic cytokine in the heart, contributes to cardiac fibrotic remodeling and dysfunction. Thus IL-4 may be a potential therapeutic target for cardiac fibrosis and dysfunction.

scholarly journals Irritable bowel syndrome: new insights into symptom mechanisms and advances in treatment

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 780 ◽  
Author(s):  
Robin Spiller
Keyword(s):  
Irritable Bowel Syndrome ◽  
New Agents ◽  
Enteric Nerves ◽  
Inflammatory Bowel ◽  
Magnetic Resonance Imaging Mri ◽  
Irritable Bowel ◽  
Fodmap Diet ◽  
And Function ◽  
The Impact

Despite being one of the most common conditions leading to gastroenterological referral, irritable bowel syndrome (IBS) is poorly understood. However, recent years have seen major advances. These include new understanding of the role of both inflammation and altered microbiota as well as the impact of dietary intolerances as illuminated by magnetic resonance imaging (MRI), which has thrown new light on IBS. This article will review new data on how excessive bile acid secretion mediates diarrhea and evidence from post infectious IBS which has shown how gut inflammation can alter gut microbiota and function. Studies of patients with inflammatory bowel disease (IBD) have also shown that even when inflammation is in remission, the altered enteric nerves and abnormal microbiota can generate IBS-like symptoms. The efficacy of the low FODMAP diet as a treatment for bloating, flatulence, and abdominal discomfort has been demonstrated by randomized controlled trials. MRI studies, which can quantify intestinal volumes, have provided new insights into how FODMAPs cause symptoms. This article will focus on these areas together with recent trials of new agents, which this author believes will alter clinical practice within the foreseeable future.

scholarly journals Peran Pendidikan Etika Kristen dalam Media Sosial di Era Disrupsi

2020 ◽  
Vol 1 (1) ◽  
pp. 38-46
Author(s):  
Mesirawati Waruwu ◽  
Yonatan Alex Arifianto ◽  
Aji Suseno
Keyword(s):  
Social Media ◽  
Ethics Education ◽  
Christian Ethics ◽  
Christian Faith ◽  
Ethical Challenges ◽  
Use Of Social Media ◽  
And Function ◽  
Meaning And Function ◽  
The Impact

The limitless development of social media, its meaning and function have begun to shift, no longer as a means of establishing relationships, communication, but at the stage of losing the role of ethics and morals, even disputes have occurred triggered by debates from communicating in social media. The purpose of this study is to describe the role of Christian ethics education in relation to the impact of social media development in the era of disruption. Using descriptive qualitative methods with literature literature can find solutions for believers in facing moral decadence due to social media abuse by knowing the era of disruption and ethical challenges from the wrong use of social media can affect moral decadence so that Christian ethics education on a biblical basis can bring modern humans. Believers in particular have become bright in social media and their use in accordance with Christian faith in this era of disruption.

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