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https://www.readbyqxmd.com/read/28716987/control-of-pathological-cardiac-hypertrophy-by-transcriptional-corepressor-irf2bp2-interferon-regulatory-factor-2-binding-protein-2
#1
Jing Fang, Tianyu Li, Xuehai Zhu, Ke-Qiong Deng, Yan-Xiao Ji, Chun Fang, Xiao-Jing Zhang, Jun-Hong Guo, Peng Zhang, Hongliang Li, Xiang Wei
The transcription factor nuclear factor of activated T-cells 1 (NFAT1), with the aid of transcriptional coactivators, has been recognized for its necessity and sufficiency to drive pathological cardiac hypertrophy. However, how the transcriptional activity of NFAT1 in terms of cardiac hypertrophy is controlled at the transcriptional level has not been well defined. Herein, we showed that a cardiac-enriched protein IRF2BP2 (interferon regulatory factor-2 binding protein 2) was further upregulated in both human and mouse hypertrophied myocardium and negatively regulated cardiomyocyte hypertrophic response in vitro...
July 17, 2017: Hypertension
https://www.readbyqxmd.com/read/28713407/biorhizome-a-biosynthetic-platform-for-colchicine-biomanufacturing
#2
REVIEW
Ganapathy Sivakumar, Kamran Alba, Gregory C Phillips
Colchicine is one of the oldest plant-based medicines used to treat gout and one of the most important alkaloid-based antimitotic drugs with anticancer potential, which is commercially extracted from Gloriosa superba. Clinical trials suggest that colchicine medication could prevent atrial fibrillation recurrence after cardiac surgery. In addition, therapeutic colchicine is undergoing clinical trials to treat non-diabetic metabolic syndrome and diabetic nephropathy. However, the industrial-scale biomanufacturing of colchicine have not yet been established...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28704447/sexual-dimorphisms-of-mrna-and-mirna-in-human-murine-heart-disease
#3
Masato Tsuji, Takanori Kawasaki, Takeru Matsuda, Tomio Arai, Satoshi Gojo, Jun K Takeuchi
BACKGROUND: Sexual dimorphisms are well recognized in various cardiac diseases such as ischemic cardiomyopathy (ICM), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Thorough understanding of the underlying genetic programs is crucial to optimize treatment strategies specified for each gender. By performing meta-analysis and microarray analysis, we sought to comprehensively characterize the sexual dimorphisms in the healthy and diseased heart at the level of both mRNA and miRNA transcriptome...
2017: PloS One
https://www.readbyqxmd.com/read/28692652/developmental-transcriptomic-analyses-for-mechanistic-insights-into-critical-pathways-involved-in-embryogenesis-of-pelagic-mahi-mahi-coryphaena-hippurus
#4
Elvis Genbo Xu, Edward M Mager, Martin Grosell, John D Stieglitz, E Starr Hazard, Gary Hardiman, Daniel Schlenk
Mahi-mahi (Coryphaena hippurus) is a commercially and ecologically important species of fish occurring in tropical and temperate waters worldwide. Understanding early life events is crucial for predicting effects of environmental stress, which is largely restricted by a lack of genetic resources regarding expression of early developmental genes and regulation of pathways. The need for anchoring developmental stages to transcriptional activities is highlighted by increasing evidence on the impacts of recurrent worldwide oil spills in this sensitive species during early development...
2017: PloS One
https://www.readbyqxmd.com/read/28671202/transcriptome-dynamics-of-human-pluripotent-stem-cell-derived-contracting-cardiomyocytes-using-an-embryoid-body-model-with-fetal-bovine-serum
#5
Kwang Bo Jung, Ye Seul Son, Hana Lee, Cho-Rok Jung, Janghwan Kim, Mi-Young Son
Cardiomyocyte (CM) differentiation techniques for generating adult-like mature CMs remain imperfect, and the plausible underlying mechanisms remain unclear; however, there are a number of current protocols available. Here, to explore the mechanisms controlling cardiac differentiation, we analyzed the genome-wide transcription dynamics occurring during the differentiation of human pluripotent stem cells (hPSCs) into CMs using embryoid body (EB) formation. We optimized and updated the protocol to efficiently generate contracting CMs from hPSCs by adding fetal bovine serum (FBS) as a medium supplement, which could have a significant impact on the efficiency of cardiac differentiation...
July 3, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28667250/heart-failure-and-mef2-transcriptome-dynamics-in-response-to-%C3%AE-blockers
#6
S W Tobin, S Hashemi, K Dadson, S Turdi, K Ebrahimian, J Zhao, G Sweeney, J Grigull, J C McDermott
Myocyte Enhancer Factor 2 (MEF2) mediates cardiac remodelling in heart failure (HF) and is also a target of β-adrenergic signalling, a front-line treatment for HF. We identified global gene transcription networks involved in HF with and without β-blocker treatment. Experimental HF by transverse aortic constriction (TAC) in a MEF2 "sensor" mouse model (6 weeks) was followed by four weeks of β-blockade with Atenolol (AT) or Solvent (Sol) treatment. Transcriptome analysis (RNA-seq) from left ventricular RNA samples and MEF2A depleted cardiomyocytes was performed...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28666990/gene-expression-profiles-for-the-identification-of-prevalent-atrial-fibrillation
#7
Sébastien Thériault, Richard Whitlock, Kripa Raman, Jessica Vincent, Salim Yusuf, Guillaume Paré
BACKGROUND: Diagnosis of atrial fibrillation (AF) can be difficult, requiring cumbersome investigations. We aimed to determine the association of established whole-blood gene expression scores with prevalent AF and to evaluate their performance for the identification of AF in a SIRS (Steroids in Cardiac Surgery) trial cohort. METHODS AND RESULTS: Whole-blood, transcriptome-wide gene expression profiling was performed using the Illumina HumanHT-12 Expression BeadChip in 416 participants (65% men) before surgery, including 91 with a diagnosis of AF...
June 30, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28663367/genome-wide-temporal-profiling-of-transcriptome-and-open-chromatin-of-early-cardiomyocyte-differentiation-derived-from-hipscs-and-hescs
#8
Qing Liu, Chao Jiang, Jin Xu, Mingtao Zhao, Kevin Van Bortle, Xun Cheng, Guangwen Wang, Howard Y Chang, Joseph C Wu, Michael P Snyder
Rationale: Recent advances have improved our ability to generate cardiomyocytes from human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). However, our understanding of the transcriptional regulatory networks underlying early stages (i.e. from mesoderm to cardiac mesoderm) of cardiomyocyte differentiation remains limited. Objective: To characterize transcriptome and chromatin accessibility during early cardiomyocyte differentiation from hiPSCs and hESCs. Methods and Results: We profiled the temporal changes in transcriptome and chromatin accessibility at genome-wide levels during cardiomyocyte differentiation derived from two hiPSC lines and two hESC lines at four stages: pluripotent stem cells, mesoderm, cardiac mesoderm, and differentiated cardiomyocytes...
June 29, 2017: Circulation Research
https://www.readbyqxmd.com/read/28654683/a-data-analysis-framework-for-biomedical-big-data-application-on-mesoderm-differentiation-of-human-pluripotent-stem-cells
#9
Benjamin Ulfenborg, Alexander Karlsson, Maria Riveiro, Caroline Améen, Karolina Åkesson, Christian X Andersson, Peter Sartipy, Jane Synnergren
The development of high-throughput biomolecular technologies has resulted in generation of vast omics data at an unprecedented rate. This is transforming biomedical research into a big data discipline, where the main challenges relate to the analysis and interpretation of data into new biological knowledge. The aim of this study was to develop a framework for biomedical big data analytics, and apply it for analyzing transcriptomics time series data from early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages...
2017: PloS One
https://www.readbyqxmd.com/read/28649439/mechanisms-of-action-of-sacubitril-valsartan-on-cardiac-remodeling-a-systems-biology-approach
#10
Oriol Iborra-Egea, Carolina Gálvez-Montón, Santiago Roura, Isaac Perea-Gil, Cristina Prat-Vidal, Carolina Soler-Botija, Antoni Bayes-Genis
Sacubitril/Valsartan, proved superiority over other conventional heart failure management treatments, but its mechanisms of action remains obscure. In this study, we sought to explore the mechanistic details for Sacubitril/Valsartan in heart failure and post-myocardial infarction remodeling, using an in silico, systems biology approach. Myocardial transcriptome obtained in response to myocardial infarction in swine was analyzed to address post-infarction ventricular remodeling. Swine transcriptome hits were mapped to their human equivalents using Reciprocal Best (blast) Hits, Gene Name Correspondence, and InParanoid database...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28646030/metabolic-remodelling-in-hypertrophied-and-failing-myocardium-a-review
#11
Mark Andrew Peterzan, Craig A Lygate, Stefan Neubauer, Oliver Rider
The energy starvation hypothesis proposes that maladaptive metabolic remodelling antedates, initiates and maintains adverse contractile dysfunction in heart failure (HF). Better understanding of the cardiac metabolic phenotype and metabolic signalling could help identify the role metabolic remodelling plays within HF and conditions known to transition toward HF, including 'pathological' hypertrophy. In this review, we discuss metabolic phenotype and metabolic signalling in the contexts of pathological hypertrophy and HF...
June 23, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28640894/characterization-and-analysis-of-long-non-coding-rna-lncrna-in-in-vitro-and-ex-vivo-derived-cardiac-progenitor-cells
#12
Baron Arnone, Jake Y Chen, Gangjian Qin
Recent advancements in cell-based therapies for the treatment of cardiovascular disease (CVD) show continuing promise for the use of transplanted stem and cardiac progenitor cells (CPCs) to promote cardiac restitution. However, a detailed understanding of the molecular mechanisms that control the development of these cells remains incomplete and is critical for optimizing their use in such therapy. Long non-coding (lnc) RNA has recently emerged as a crucial class of regulatory molecules involved in directing a variety of critical biological processes including development, homeostasis and disease...
2017: PloS One
https://www.readbyqxmd.com/read/28640452/role-of-epicardial-adipose-tissue-in-health-and-disease-a-matter-of-fat
#13
Bénédicte Gaborit, Coralie Sengenes, Patricia Ancel, Alexis Jacquier, Anne Dutour
Epicardial adipose tissue (EAT) is a small but very biologically active ectopic fat depot that surrounds the heart. Given its rapid metabolism, thermogenic capacity, unique transcriptome, secretory profile, and simply measurability, epicardial fat has drawn increasing attention among researchers attempting to elucidate its putative role in health and cardiovascular diseases. The cellular crosstalk between epicardial adipocytes and cells of the vascular wall or myocytes is high and suggests a local role for this tissue...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28637782/the-brugada-syndrome-susceptibility-gene-hey2-modulates-cardiac-transmural-ion-channel-patterning-and-electrical-heterogeneity
#14
Christiaan C Veerman, Svitlana Podliesna, Rafik Tadros, Elisabeth M Lodder, Isabella Mengarelli, Berend de Jonge, Leander Beekman, Julien Barc, Ronald Wilders, Arthur A Wilde, Bastiaan J Boukens, Ruben Coronel, Arie Verkerk, Carol Ann Remme, Connie R Bezzina
Rationale: Genome-wide association studies previously identified an association of rs9388451 at chromosome 6q22.3 (near HEY2) with Brugada syndrome (BrS). The causal gene and underlying mechanism remain unresolved. Objective: We used an integrative approach entailing transcriptomic studies in human hearts and electrophysiological studies in Hey2 heterozygous knockout mice (Hey2(+/-) ) to dissect the underpinnings of the 6q22.31 association with BrS. Methods and Results: We queried expression quantitative trait locus (eQTL) data acquired in 190 human left ventricular (LV) samples from the Genotype-Tissue Expression (GTEx) consortium for cis-eQTL effects of rs9388451 which revealed an association between BrS risk allele dosage and HEY2 expression (β=+0...
June 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28632131/reciprocal-analyses-in-zebrafish-and-medaka-reveal-that-harnessing-the-immune-response-promotes-cardiac-regeneration
#15
Shih-Lei Lai, Rubén Marín-Juez, Pedro Luís Moura, Carsten Kuenne, Jason Kuan Han Lai, Ayele Taddese Tsedeke, Stefan Guenther, Mario Looso, Didier Yr Stainier
Zebrafish display a distinct ability to regenerate their heart following injury. However, this ability is not shared by another teleost, the medaka. In order to identify cellular and molecular bases for this difference, we performed comparative transcriptomic analyses following cardiac cryoinjury. This comparison points to major differences in immune cell dynamics between these models. Upon closer examination, we observed delayed and reduced macrophage recruitment in medaka, along with delayed neutrophil clearance...
June 20, 2017: ELife
https://www.readbyqxmd.com/read/28626076/cardiac-fibroblast-transcriptome-analyses-support-a-role-for-interferogenic-profibrotic-and-inflammatory-genes-in-anti-ssa-ro-associated-congenital-heart-block
#16
Robert M Clancy, Androo J Markham, Tanisha Jackson, Sara E Rasmussen, Miroslav Blumenberg, Jill P Buyon
The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated hY3. The top ten upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response (e...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28614664/molecular-mechanisms-of-developmental-toxicity-induced-by-graphene-oxide-at-predicted-environmental-concentrations
#17
Xingli Zhang, Qixing Zhou, Wei Zou, Xiangang Hu
Developmental toxicity is a critical issue in nanotoxicity. However, very little is known about the effects of graphene oxide (GO, a widely used carbon material) at predicted environmental concentrations on biological development or the specific molecular mechanisms. The present study established that the development of zebrafish embryos exposed to trace concentrations (1-100 μg/L) of GO was impaired because of DNA modification, protein carbonylation and excessive generation of reactive oxygen species (ROS), especially the superoxide radical...
June 28, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28611032/genome-wide-dynamics-of-nascent-noncoding-rna-transcription-in-porcine-heart-after-myocardial-infarction
#18
Minna U Kaikkonen, Paavo Halonen, Oscar Hsin-Fu Liu, Tiia A Turunen, Juho Pajula, Pierre Moreau, Ilakya Selvarajan, Tomi Tuomainen, Einari Aavik, Pasi Tavi, Seppo Ylä-Herttuala
BACKGROUND: Microarrays and RNA sequencing are widely used to profile transcriptome remodeling during myocardial ischemia. However, the steady-state RNA analysis lacks in sensitivity to detect all noncoding RNA species and does not provide separation between transcriptional and post-transcriptional regulations. Here, we provide the first comprehensive analysis of nascent RNA profiles of mRNAs, primary micro-RNAs, long noncoding RNAs, and enhancer RNAs in a large animal model of acute infarction...
June 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28588076/pai-1-controls-cardiomyocyte-tgf-%C3%AE-and-cardiac-fibrosis
#19
Panagiotis Flevaris, Sadiya S Khan, Mesut Eren, Adam J Schuldt, Sanjiv J Shah, Daniel C Lee, Sweta Gupta, Amy Shapiro, Paul Burridge, Asish K Ghosh, Douglas E Vaughan
Background -Fibrosis is the pathologic consequence of stress-induced tissue remodeling and matrix accumulation. Increased levels of plasminogen activator inhibitor type I (PAI-1) have been shown to promote fibrosis in multiple organ systems. Paradoxically, homozygous genetic deficiency of PAI-1 is associated with spontaneous age-dependent cardiac-selective fibrosis in mice. We have identified a novel PAI-1-dependent mechanism that regulates cardiomyocyte-derived fibrogenic signals and cardiac transcriptional pathways during injury...
June 6, 2017: Circulation
https://www.readbyqxmd.com/read/28567671/downregulation-of-the-complement-cascade-in-vitro-in-mice-and-in-patients-with-cardiovascular-disease-by-the-bet-protein-inhibitor-apabetalone-rvx-208
#20
Sylwia Wasiak, Dean Gilham, Laura M Tsujikawa, Christopher Halliday, Cyrus Calosing, Ravi Jahagirdar, Jan Johansson, Michael Sweeney, Norman C Wong, Ewelina Kulikowski
Apabetalone (RVX-208) is an epigenetic regulator developed to treat cardiovascular disease (CVD) that targets BET proteins. Through transcriptional regulation RVX-208 modulates pathways that underlie CVD including reverse cholesterol transport, vascular inflammation, coagulation, and complement. Using transcriptomics and proteomics we show that complement is one of the top pathways downregulated by RVX-208 in primary human hepatocytes (PHH) and in plasma from CVD patients. RVX-208 reduces basal and cytokine-driven expression of complement factors in PHH and in chimeric mice with humanized livers...
May 31, 2017: Journal of Cardiovascular Translational Research
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