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Cardiac epigenomics

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https://www.readbyqxmd.com/read/28526543/thyroid-hormone-biosynthesis-machinery-is-altered-in-the-ischemic-myocardium-an-epigenomic-study
#1
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...
May 11, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28515341/bet-bromodomain-inhibition-suppresses-innate-inflammatory-and-profibrotic-transcriptional-networks-in-heart-failure
#2
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
#3
Shanshan Ai, Xianhong Yu, Yumei Li, Yong Peng, Chen Li, Yanzhu Yue, Ge Tao, Chuan-Yun Li, William T Pu, Aibin He
Rationale: Polycomb repressive complex 2 (PRC2) 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 two 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. Methods and Results: Heart development was normal in Ezh1(-/-) (E1KO) and Ezh2(f/f)::cTNT(-Cre) (E2KO) embryos...
May 16, 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27754176/sy-15-2-endothelial-epigenetics-and-its-role-in-mediating-biomechanical-stress-of-hypertension
#10
Peter F Davies, Elisabetta Manduchi, Christian J Stoeckert, Yi-Zhou Jiang
Hemodynamics creates a constantly changing physical and chemical environment to which the arterial endothelium is exquisitely sensitive. Biomechanical stresses are intrinsic to blood flow characteristics and blood pressure and therefore are important considerations in hypertension. Near branching anatomical sites in arteries, blood flow separates from the main flow to undergo complex multi-directional characteristics for a part of each cardiac cycle (collectively referred to as disturbed flow). Atherosclerosis and aneurysmal pathology develop preferentially at disturbed flow locations, particularly when an additional cardiovascular risk factor such as hypercholesterolemia or high blood pressure are present...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27703156/genome-wide-compendium-and-functional-assessment-of-in-vivo-heart-enhancers
#11
Diane E Dickel, Iros Barozzi, Yiwen Zhu, Yoko Fukuda-Yuzawa, Marco Osterwalder, Brandon J Mannion, Dalit May, Cailyn H Spurrell, Ingrid Plajzer-Frick, Catherine S Pickle, Elizabeth Lee, Tyler H Garvin, Momoe Kato, Jennifer A Akiyama, Veena Afzal, Ah Young Lee, David U Gorkin, Bing Ren, Edward M Rubin, Axel Visel, Len A Pennacchio
Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of >35 epigenomic data sets from mouse and human pre- and postnatal hearts we created a comprehensive reference of >80,000 putative human heart enhancers...
October 5, 2016: Nature Communications
https://www.readbyqxmd.com/read/27671623/low-concentrations-of-bromodichloromethane-induce-a-toxicogenomic-response-in-porcine-embryos-in-vitro
#12
Florence Pagé-Larivière, Amélie Tremblay, Céline Campagna, Manuel J Rodriguez, Marc-André Sirard
Bromodichloromethane (BDCM) is one of the trihalomethanes present in chlorinated water. Humans are thus daily exposed. Previous contradictory results failed to clearly establish the adverse effects of low concentrations of BDCM. By using the porcine preimplantation embryo as a sensitive model, we showed that exposure to low concentrations of BDCM (10 and 100ppb) during the first week of embryo development induced adverse effect on the blastocyst rate and alteration of the estradiol pathway. Our results also suggest that blastocysts exposed to BDCM present transcriptomic and epigenomic adaptive modifications compatible with the cardiac anomalies observed by previous studies of newborns exposed to BDCM during gestation...
September 23, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27634651/epigenome-wide-association-study-reveals-differential-dna-methylation-in-individuals-with-a-history-of-myocardial-infarction
#13
Mathias Rask-Andersen, David Martinsson, Muhammad Ahsan, Stefan Enroth, Weronica E Ek, Ulf Gyllensten, Åsa Johansson
Cardiovascular diseases (CVDs) are the leading causes of death worldwide and represent a substantial economic burden on public health care systems. Epigenetic markers have potential as diagnostic markers before clinical symptoms have emerged, and as prognostic markers to inform the choice of clinical intervention. In this study, we performed an epigenome-wide association study (EWAS) for CVDs, to identify disease-specific alterations in DNA methylation. CpG methylation in blood samples from the northern Sweden population health study (NSPHS) (n = 729) was assayed on the Illumina Infinium HumanMethylation450 BeadChip...
September 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27622691/single-cell-transcriptome-and-epigenomic-reprogramming-of-cardiomyocyte-derived-cardiac-progenitor-cells
#14
COMMENT
Xin Chen, Tushar Chakravarty, Yiqiang Zhang, Xiaojin Li, Jiang F Zhong, Charles Wang
The molecular basis underlying the dedifferentiation of mammalian adult cardiomyocytes (ACMs) into myocyte-derived cardiac progenitor cells (mCPCs) during cardiac tissue regeneration is poorly understood. We present data integrating single-cell transcriptome and whole-genome DNA methylome analyses of mouse mCPCs to understand the epigenomic reprogramming governing their intrinsic cellular plasticity. Compared to parental cardiomyocytes, mCPCs display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome...
September 13, 2016: Scientific Data
https://www.readbyqxmd.com/read/27502479/a-simplified-langendorff-free-method-for-concomitant-isolation-of-viable-cardiac-myocytes-and-nonmyocytes-from-the-adult-mouse-heart
#15
Matthew Ackers-Johnson, Peter Yiqing Li, Andrew P Holmes, Sian-Marie O'Brien, Davor Pavlovic, Roger S Foo
RATIONALE: Cardiovascular disease represents a global pandemic. The advent of and recent advances in mouse genomics, epigenomics, and transgenics offer ever-greater potential for powerful avenues of research. However, progress is often constrained by unique complexities associated with the isolation of viable myocytes from the adult mouse heart. Current protocols rely on retrograde aortic perfusion using specialized Langendorff apparatus, which poses considerable logistical and technical barriers to researchers and demands extensive training investment...
September 30, 2016: Circulation Research
https://www.readbyqxmd.com/read/27496870/comparative-dna-methylation-and-gene-expression-analysis-identifies-novel-genes-for-structural-congenital-heart-diseases
#16
Marcel Grunert, Cornelia Dorn, Huanhuan Cui, Ilona Dunkel, Kerstin Schulz, Sophia Schoenhals, Wei Sun, Felix Berger, Wei Chen, Silke R Sperling
AIMS: For the majority of congenital heart diseases (CHDs), the full complexity of the causative molecular network, which is driven by genetic, epigenetic, and environmental factors, is yet to be elucidated. Epigenetic alterations are suggested to play a pivotal role in modulating the phenotypic expression of CHDs and their clinical course during life. Candidate approaches implied that DNA methylation might have a developmental role in CHD and contributes to the long-term progress of non-structural cardiac diseases...
October 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27226577/reciprocal-regulation-of-the-cardiac-epigenome-by-chromatin-structural-proteins-hmgb-and-ctcf-implications-for-transcriptional-regulation
#17
Emma Monte, Manuel Rosa-Garrido, Elaheh Karbassi, Haodong Chen, Rachel Lopez, Christoph D Rau, Jessica Wang, Stanley F Nelson, Yong Wu, Enrico Stefani, Aldons J Lusis, Yibin Wang, Siavash K Kurdistani, Sarah Franklin, Thomas M Vondriska
Transcriptome remodeling in heart disease occurs through the coordinated actions of transcription factors, histone modifications, and other chromatin features at pathology-associated genes. The extent to which genome-wide chromatin reorganization also contributes to the resultant changes in gene expression remains unknown. We examined the roles of two chromatin structural proteins, Ctcf (CCCTC-binding factor) and Hmgb2 (high mobility group protein B2), in regulating pathologic transcription and chromatin remodeling...
July 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27162171/discovery-and-validation-of-sub-threshold-genome-wide-association-study-loci-using-epigenomic-signatures
#18
Xinchen Wang, Nathan R Tucker, Gizem Rizki, Robert Mills, Peter Hl Krijger, Elzo de Wit, Vidya Subramanian, Eric Bartell, Xinh-Xinh Nguyen, Jiangchuan Ye, Jordan Leyton-Mange, Elena V Dolmatova, Pim van der Harst, Wouter de Laat, Patrick T Ellinor, Christopher Newton-Cheh, David J Milan, Manolis Kellis, Laurie A Boyer
Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability, suggesting that meaningful associations lie 'hidden' below current thresholds. Here, we integrate information from association studies with epigenomic maps to demonstrate that enhancers significantly overlap known loci associated with the cardiac QT interval and QRS duration. We apply functional criteria to identify loci associated with QT interval that do not meet genome-wide significance and are missed by existing studies...
May 10, 2016: ELife
https://www.readbyqxmd.com/read/27105846/isl1-and-jmjd3-synergistically-control-cardiac-differentiation-of-embryonic-stem-cells
#19
Yang Wang, Yuejiao Li, Chen Guo, Qin Lu, Weiping Wang, Zhuqing Jia, Ping Chen, Kangtao Ma, Danny Reinberg, Chunyan Zhou
ISL1 is expressed in cardiac progenitor cells and plays critical roles in cardiac lineage differentiation and heart development. Cardiac progenitor cells hold great potential for clinical and translational applications. However, the mechanisms underlying ISL1 function in cardiac progenitor cells have not been fully elucidated. Here we uncover a hierarchical role of ISL1 in cardiac progenitor cells, showing that ISL1 directly regulates hundreds of potential downstream target genes that are implicated in cardiac differentiation, through an epigenetic mechanism...
August 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27054504/transcriptome-analysis-in-heart-failure
#20
REVIEW
Scot J Matkovich
PURPOSE OF REVIEW: Genome-wide analysis of RNA abundances (transcriptome analysis) offers great potential to identify biomarkers of disease and to gain insight into mechanisms underlying the development of heart failure. I will discuss key factors in generating and evaluating transcriptome data, and recent studies that have contributed to the understanding of cardiac disease in humans and animal models. RECENT FINDINGS: Thorough assessments of RNA-sequencing performance performed across multiple laboratories have demonstrated its primacy in measuring differential RNA abundances, due in part to its wide dynamic range and accuracy...
May 2016: Current Opinion in Cardiology
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