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Cardiac epigenomics

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https://www.readbyqxmd.com/read/29667349/asb1-differential-methylation-in-ischaemic-cardiomyopathy-relationship-with-left-ventricular-performance-in-end-stage-heart-failure-patients
#1
Ana Ortega, Estefanía Tarazón, Carolina Gil-Cayuela, Luis Martínez-Dolz, Francisca Lago, José Ramón González-Juanatey, Juan Sandoval, Manuel Portolés, Esther Roselló-Lletí, Miguel Rivera
AIMS: Ischaemic cardiomyopathy (ICM) leads to impaired contraction and ventricular dysfunction, causing high rates of morbidity and mortality. Epigenomics allows the identification of epigenetic signatures in human diseases. We analyse the differential epigenetic patterns of the ASB gene family in ICM patients and relate these alterations to their haemodynamic and functional status. METHODS AND RESULTS: Epigenomic analysis was carried out using 16 left ventricular (LV) tissue samples, eight from ICM patients undergoing heart transplantation and eight from control (CNT) subjects without cardiac disease...
April 17, 2018: ESC Heart Failure
https://www.readbyqxmd.com/read/29593016/gcat-genomes-for-life-a-prospective-cohort-study-of-the-genomes-of-catalonia
#2
Mireia Obón-Santacana, Mireia Vilardell, Anna Carreras, Xavier Duran, Juan Velasco, Iván Galván-Femenía, Teresa Alonso, Lluís Puig, Lauro Sumoy, Eric J Duell, Manuel Perucho, Victor Moreno, Rafael de Cid
PURPOSE: The prevalence of chronic non-communicable diseases (NCDs) is increasing worldwide. NCDs are the leading cause of both morbidity and mortality, and it is estimated that by 2030, they will be responsible for 80% of deaths across the world. The Genomes for Life (GCAT) project is a long-term prospective cohort study that was designed to integrate and assess the role of epidemiological, genomic and epigenomic factors in the development of major chronic diseases in Catalonia, a north-east region of Spain...
March 27, 2018: BMJ Open
https://www.readbyqxmd.com/read/29540468/genetic-reduction-in-left-ventricular-protein-kinase-c-%C3%AE-and-adverse-ventricular-remodeling-in-human-subjects
#3
Ray Hu, Michael P Morley, Jeffrey Brandimarto, Nathan R Tucker, Victoria A Parsons, Sihai D Zhao, Benjamin Meder, Hugo A Katus, Frank Rühle, Monika Stoll, Eric Villard, François Cambien, Honghuang Lin, Nicholas L Smith, Janine F Felix, Ramachandran S Vasan, Pim van der Harst, Christopher Newton-Cheh, Jin Li, Cecilia E Kim, Hakon Hakonarson, Sridhar Hannenhalli, Euan A Ashley, Christine S Moravec, W H Wilson Tang, Marjorie Maillet, Jeffery D Molkentin, Patrick T Ellinor, Kenneth B Margulies, Thomas P Cappola
BACKGROUND: Inhibition of PKC-α (protein kinase C-α) enhances contractility and cardioprotection in animal models, but effects in humans are unknown. Genotypes at rs9912468 strongly associate with PRKCA expression in the left ventricle, enabling genetic approaches to measure effects of reduced PKC-α in human populations. METHODS AND RESULTS: We analyzed the cis expression quantitative trait locus for PRKCA marked by rs9912468 using 313 left ventricular specimens from European Ancestry patients...
March 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29499155/setd7-drives-cardiac-lineage-commitment-through-stage-specific-transcriptional-activation
#4
Jaecheol Lee, Ning-Yi Shao, David T Paik, Haodi Wu, Hongchao Guo, Vittavat Termglinchan, Jared M Churko, Youngkyun Kim, Tomoya Kitani, Ming-Tao Zhao, Yue Zhang, Kitchener D Wilson, Ioannis Karakikes, Michael P Snyder, Joseph C Wu
Cardiac development requires coordinated and large-scale rearrangements of the epigenome. The roles and precise mechanisms through which specific epigenetic modifying enzymes control cardiac lineage specification, however, remain unclear. Here we show that the H3K4 methyltransferase SETD7 controls cardiac differentiation by reading H3K36 marks independently of its enzymatic activity. Through chromatin immunoprecipitation sequencing (ChIP-seq), we found that SETD7 targets distinct sets of genes to drive their stage-specific expression during cardiomyocyte differentiation...
March 1, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29374152/distinct-epigenetic-programs-regulate-cardiac-myocyte-development-and-disease-in-the-human-heart-in-vivo
#5
Ralf Gilsbach, Martin Schwaderer, Sebastian Preissl, Björn A Grüning, David Kranzhöfer, Pedro Schneider, Thomas G Nührenberg, Sonia Mulero-Navarro, Dieter Weichenhan, Christian Braun, Martina Dreßen, Adam R Jacobs, Harald Lahm, Torsten Doenst, Rolf Backofen, Markus Krane, Bruce D Gelb, Lutz Hein
Epigenetic mechanisms and transcription factor networks essential for differentiation of cardiac myocytes have been uncovered. However, reshaping of the epigenome of these terminally differentiated cells during fetal development, postnatal maturation, and in disease remains unknown. Here, we investigate the dynamics of the cardiac myocyte epigenome during development and in chronic heart failure. We find that prenatal development and postnatal maturation are characterized by a cooperation of active CpG methylation and histone marks at cis-regulatory and genic regions to shape the cardiac myocyte transcriptome...
January 26, 2018: Nature Communications
https://www.readbyqxmd.com/read/29321036/maternal-engineered-nanomaterial-inhalation-during-gestation-alters-the-fetal-transcriptome
#6
P A Stapleton, Q A Hathaway, C E Nichols, A B Abukabda, M V Pinti, D L Shepherd, C R McBride, J Yi, V C Castranova, J M Hollander, T R Nurkiewicz
BACKGROUND: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation...
January 10, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29052586/corrigendum-epigenomic-reprogramming-of-adult-cardiomyocyte-derived-cardiac-progenitor-cells
#7
Yiqiang Zhang, Jiang F Zhong, Hongyu Qiu, W Robb MacLellan, Eduardo Marbán, Charles Wang
This corrects the article DOI: 10.1038/srep17686.
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29026447/epigenome-alterations-in-aortic-valve-stenosis-and-its-related-left-ventricular-hypertrophy
#8
REVIEW
Igor Gošev, Martina Zeljko, Željko Đurić, Ivana Nikolić, Milorad Gošev, Sanja Ivčević, Dino Bešić, Zoran Legčević, Frane Paić
Aortic valve stenosis is the most common cardiac valve disease, and with current trends in the population demographics, its prevalence is likely to rise, thus posing a major health and economic burden facing the worldwide societies. Over the past decade, it has become more than clear that our traditional genetic views do not sufficiently explain the well-known link between AS, proatherogenic risk factors, flow-induced mechanical forces, and disease-prone environmental influences. Recent breakthroughs in the field of epigenetics offer us a new perspective on gene regulation, which has broadened our perspective on etiology of aortic stenosis and other aortic valve diseases...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28859577/single-cell-sequencing-technologies-for-cardiac-stem-cell-studies
#9
Tiantian Liu, Hongjin Wu, Shixiu Wu, Charles Wang
Today with the rapid advancements in stem cell studies and the promising potential of using stem cells in clinical therapy, there is an increasing demand for in-depth comprehensive analysis on individual cell transcriptome and epigenome, as they play critical roles in a number of cell functions such as cell differentiation, growth, and reprogramming. The development of single-cell sequencing technologies has helped in revealing some exciting new perspectives in stem cells and regenerative medicine research...
November 1, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28838933/epigenome-wide-association-study-identifies-cardiac-gene-patterning-and-a-novel-class-of-biomarkers-for-heart-failure
#10
Benjamin Meder, Jan Haas, Farbod Sedaghat-Hamedani, Elham Kayvanpour, Karen Frese, Alan Lai, Rouven Nietsch, Christina Scheiner, Stefan Mester, Diana Martins Bordalo, Ali Amr, Carsten Dietrich, Dietmar Pils, Dominik Siede, Hauke Hund, Andrea Bauer, Daniel Benjamin Holzer, Arjang Ruhparwar, Matthias Mueller-Hennessen, Dieter Weichenhan, Christoph Plass, Tanja Weis, Johannes Backs, Maximilian Wuerstle, Andreas Keller, Hugo A Katus, Andreas E Posch
BACKGROUND: Biochemical DNA modification resembles a crucial regulatory layer among genetic information, environmental factors, and the transcriptome. To identify epigenetic susceptibility regions and novel biomarkers linked to myocardial dysfunction and heart failure, we performed the first multi-omics study in myocardial tissue and blood of patients with dilated cardiomyopathy and controls. METHODS: Infinium human methylation 450 was used for high-density epigenome-wide mapping of DNA methylation in left-ventricular biopsies and whole peripheral blood of living probands...
October 17, 2017: Circulation
https://www.readbyqxmd.com/read/28802249/high-resolution-mapping-of-chromatin-conformation-in-cardiac-myocytes-reveals-structural-remodeling-of-the-epigenome-in-heart-failure
#11
Manuel Rosa-Garrido, Douglas J Chapski, Anthony D Schmitt, Todd H Kimball, Elaheh Karbassi, Emma Monte, Enrique Balderas, Matteo Pellegrini, Tsai-Ting Shih, Elizabeth Soehalim, David Liem, Peipei Ping, Niels J Galjart, Shuxun Ren, Yibin Wang, Bing Ren, Thomas M Vondriska
BACKGROUND: Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. METHODS: To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype...
October 24, 2017: Circulation
https://www.readbyqxmd.com/read/28526543/thyroid-hormone-biosynthesis-machinery-is-altered-in-the-ischemic-myocardium-an-epigenomic-study
#12
Carolina Gil-Cayuela, Esther Roselló-LLetí, Estefanía Tarazón, Ana Ortega, Juan Sandoval, Luis Martínez-Dolz, Juan Cinca, Esther Jorge, José Ramón González-Juanatey, Francisca Lago, Miguel Rivera, Manuel Portolés
BACKGROUND: Abnormal thyroid hormone (TH) metabolism is significantly associated with impaired left ventricular (LV) function and death. Although TH was traditionally thought to be produced exclusively by the thyroid gland, an increasing number of studies report TH production in other tissues. Based on these findings, we evaluated whether the genes required for TH biosynthesis are expressed in the human heart, and whether their expression is altered in patients with ischemic cardiomyopathy (ICM) and is related to epigenetic variations...
September 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28515341/bet-bromodomain-inhibition-suppresses-innate-inflammatory-and-profibrotic-transcriptional-networks-in-heart-failure
#13
Qiming Duan, Sarah McMahon, Priti Anand, Hirsh Shah, Sean Thomas, Hazel T Salunga, Yu Huang, Rongli Zhang, Aarathi Sahadevan, Madeleine E Lemieux, Jonathan D Brown, Deepak Srivastava, James E Bradner, Timothy A McKinsey, Saptarsi M Haldar
Despite current standard of care, the average 5-year mortality after an initial diagnosis of heart failure (HF) is about 40%, reflecting an urgent need for new therapeutic approaches. Previous studies demonstrated that the epigenetic reader protein bromodomain-containing protein 4 (BRD4), an emerging therapeutic target in cancer, functions as a critical coactivator of pathologic gene transactivation during cardiomyocyte hypertrophy. However, the therapeutic relevance of these findings to human disease remained unknown...
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28512107/divergent-requirements-for-ezh1-in-heart-development-versus-regeneration
#14
COMPARATIVE STUDY
Shanshan Ai, Xianhong Yu, Yumei Li, Yong Peng, Chen Li, Yanzhu Yue, Ge Tao, Chuanyun Li, William T Pu, Aibin He
RATIONALE: Polycomb repressive complex 2 is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are 2 alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. OBJECTIVE: We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration...
July 7, 2017: Circulation Research
https://www.readbyqxmd.com/read/28460026/epigenomic-and-transcriptomic-approaches-in-the-post-genomic-era-path-to-novel-targets-for-diagnosis-and-therapy-of-the-ischaemic-heart-position-paper-of-the-european-society-of-cardiology-working-group-on-cellular-biology-of-the-heart
#15
REVIEW
Cinzia Perrino, Albert-Laszló Barabási, Gianluigi Condorelli, Sean Michael Davidson, Leon De Windt, Stefanie Dimmeler, Felix Benedikt Engel, Derek John Hausenloy, Joseph Addison Hill, Linda Wilhelmina Van Laake, Sandrine Lecour, Jonathan Leor, Rosalinda Madonna, Manuel Mayr, Fabrice Prunier, Joost Petrus Geradus Sluijter, Rainer Schulz, Thomas Thum, Kirsti Ytrehus, Péter Ferdinandy
Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets...
June 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28075199/an-epigenome-wide-association-analysis-of-cardiac-autonomic-responses-among-a-population-of-welders
#16
Jinming Zhang, Zhonghua Liu, Peter E Umukoro, Jennifer M Cavallari, Shona C Fang, Marc G Weisskopf, Xihong Lin, Murray A Mittleman, David C Christiani
DNA methylation is one of the potential epigenetic mechanisms associated with various adverse cardiovascular effects; however, its association with cardiac autonomic dysfunction, in particular, is unknown. In the current study, we aimed to identify epigenetic variants associated with alterations in cardiac autonomic responses. Cardiac autonomic responses were measured with two novel markers: acceleration capacity (AC) and deceleration capacity (DC). We examined DNA methylation levels at more than 472,506 CpG probes through the Illumina Infinium HumanMethylation450 BeadChip assay...
February 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28055289/cardiovascular-diseases-interplay-of-epigenetics
#17
REVIEW
Yog R Ahuja, Sanjeev Sharma, Vasavi Mohan
Several association studies have been carried out to elucidate the role of genetic variants in cardiovascular diseases (CVDs), while studies on the epigenome regulating gene expression changes are helping to understand the development of disease and factors promoting such changes. This review summarizes the different epigenetic aspects involved in cardiac development and disease along with current therapeutic interventions.
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28052262/neil3-dependent-regulation-of-cardiac-fibroblast-proliferation-prevents-myocardial-rupture
#18
Maria B Olsen, Gunn A Hildrestrand, Katja Scheffler, Leif Erik Vinge, Katrine Alfsnes, Vuk Palibrk, Junbai Wang, Christine G Neurauter, Luisa Luna, Jostein Johansen, Jonas D S Øgaard, Ingrid K Ohm, Geir Slupphaug, Anna Kuśnierczyk, Arnt E Fiane, Sverre-Henning Brorson, Lili Zhang, Lars Gullestad, William E Louch, Per Ole Iversen, Ingunn Østlie, Arne Klungland, Geir Christensen, Ivar Sjaastad, Pål Sætrom, Arne Yndestad, Pål Aukrust, Magnar Bjørås, Alexandra V Finsen
Myocardial infarction (MI) triggers a reparative response involving fibroblast proliferation and differentiation driving extracellular matrix modulation necessary to form a stabilizing scar. Recently, it was shown that a genetic variant of the base excision repair enzyme NEIL3 was associated with increased risk of MI in humans. Here, we report elevated myocardial NEIL3 expression in heart failure patients and marked myocardial upregulation of Neil3 after MI in mice, especially in a fibroblast-enriched cell fraction...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/27981795/targeting-the-epigenome-screening-bioactive-compounds-that-regulate-histone-deacetylase-activity
#19
Luis D Godoy, Julianna E Lucas, Abigail J Bender, Samantha S Romanick, Bradley S Ferguson
SCOPE: Nutrigenomics is a rapidly expanding field that elucidates the link between diet-genome interactions. Recent evidence demonstrates that regulation of the epigenome, and in particular inhibition of histone deacetylases (HDACs), impact pathogenetic mechanisms involved in chronic disease. Few studies, to date, have screened libraries of bioactive compounds that act as epigenetic modifiers. This study screened a library of 131 natural compounds to determine bioactive compounds that inhibit Zn-dependent HDAC activity...
April 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27893464/the-h3k9-dimethyltransferases-ehmt1-2-protect-against-pathological-cardiac-hypertrophy
#20
Bernard Thienpont, Jan Magnus Aronsen, Emma Louise Robinson, Hanneke Okkenhaug, Elena Loche, Arianna Ferrini, Patrick Brien, Kanar Alkass, Antonio Tomasso, Asmita Agrawal, Olaf Bergmann, Ivar Sjaastad, Wolf Reik, Hywel Llewelyn Roderick
Cardiac hypertrophic growth in response to pathological cues is associated with reexpression of fetal genes and decreased cardiac function and is often a precursor to heart failure. In contrast, physiologically induced hypertrophy is adaptive, resulting in improved cardiac function. The processes that selectively induce these hypertrophic states are poorly understood. Here, we have profiled 2 repressive epigenetic marks, H3K9me2 and H3K27me3, which are involved in stable cellular differentiation, specifically in cardiomyocytes from physiologically and pathologically hypertrophied rat hearts, and correlated these marks with their associated transcriptomes...
January 3, 2017: Journal of Clinical Investigation
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