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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
#1
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/28632131/reciprocal-analyses-in-zebrafish-and-medaka-reveal-that-harnessing-the-immune-response-promotes-cardiac-regeneration
#2
Didier Yr Stainier, Shih-Lei Ben Lai, Rubén Marín-Juez, Pedro Luís Moura, Carsten Kuenne, Jason Kuan Han Lai, Ayele Taddese Tsedeke, Stefan Guenther, Mario Looso
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
#3
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
#4
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 14, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28611032/genome-wide-dynamics-of-nascent-noncoding-rna-transcription-in-porcine-heart-after-myocardial-infarction
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28542617/inflammatory-and-apoptotic-remodeling-in-autonomic-nervous-system-following-myocardial-infarction
#8
Chen Gao, Kimberly Howard-Quijano, Christoph Rau, Tatsuo Takamiya, Yang Song, Kalyanam Shivkumar, Yibin Wang, Aman Mahajan
BACKGROUND: Chronic myocardial infarction (MI) triggers pathological remodeling in the heart and cardiac nervous system. Abnormal function of the autonomic nervous system (ANS), including stellate ganglia (SG) and dorsal root ganglia (DRG) contribute to increased sympathoexcitation, cardiac dysfunction and arrythmogenesis. ANS modulation is a therapeutic target for arrhythmia associated with cardiac injury. However, the molecular mechanism involved in the pathological remodeling in ANS following cardiac injury remains to be established...
2017: PloS One
https://www.readbyqxmd.com/read/28538179/hand2-target-gene-regulatory-networks-control-atrioventricular-canal-and-cardiac-valve-development
#9
Frédéric Laurent, Ausra Girdziusaite, Julie Gamart, Iros Barozzi, Marco Osterwalder, Jennifer A Akiyama, Joy Lincoln, Javier Lopez-Rios, Axel Visel, Aimée Zuniga, Rolf Zeller
The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28536000/an-analysis-of-myod-dependent-transcription-using-crispr-cas9-gene-targeting-in-xenopus-tropicalis-embryos
#10
Caitlin McQueen, Mary Elizabeth Pownall
Myogenic regulatory factors (MRFs) are known to have essential roles in both the establishment and differentiation of the skeletal muscle cell lineage. MyoD is expressed early in the Xenopus mesoderm where it is present and active several hours before the activation of muscle differentiation genes. Previous studies in cultured cells and in Xenopus laevis have identified sets of genes that require MyoD prior to differentiation of skeletal muscle. Here we report results from experiments using CRISPR/Cas9 to target the MyoD gene in the diploid frog Xenopus tropicalis, that are analysed by RNA-seq at gastrula stages...
May 20, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28515341/bet-bromodomain-inhibition-suppresses-innate-inflammatory-and-profibrotic-transcriptional-networks-in-heart-failure
#11
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/28514806/human-epicardial-fat-expresses-glucagon-like-peptide-1-and-2-receptors-genes
#12
Gianluca Iacobellis, Vladimir Camarena, David W Sant, Gaofeng Wang
Epicardial adipose tissue (EAT) is an easily measurable visceral fat of the heart with unique anatomy, functionality, and transcriptome. EAT can serve as a therapeutic target for pharmaceutical agents targeting the fat. Glucagon-like peptide-1 (GLP-1) and GLP-2 analogues are newer drugs showing beneficial cardiovascular and metabolic effects. Whether EAT expresses GLP- 1 and 2 receptors (GLP-1R and GLP-2R) is unknown. RNA-seq analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to evaluate the presence of GLP-1R and GLP-2R in EAT and subcutaneous fat (SAT) obtained from 8 subjects with coronary artery disease and type 2 diabetes mellitus undergoing elective cardiac surgery...
May 17, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28512107/divergent-requirements-for-ezh1-in-heart-development-versus-regeneration
#13
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/28500252/transcriptome-profiling-reveals-novel-bmi-and-sex-specific-gene-expression-signature-for-human-cardiac-hypertrophy
#14
Mackenzie S Newman, Tina Nguyen, Michael J Watson, Robert Hull, Han-Gang Yu
BACKGROUND: How obesity or sex may affect the gene expression profiles of human cardiac hypertrophy is unknown. We hypothesized that body-mass index (BMI) and sex can affect gene expression profiles of cardiac hypertrophy. RESULTS: Human heart tissues were grouped according to sex (male, female), BMI (lean<25 kg/m(2), obese>30 kg/m(2)), or left ventricular hypertrophy (LVH) and non-LVH non-failed controls (NF). We identified 24 DE genes comparing female to male samples...
May 12, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28500173/tgf-%C3%AE-1-transforming-growth-factor-%C3%AE-1-plays-a-pivotal-role-in-cardiac-myofibroblast-arrhythmogenicity
#15
Nicolò Salvarani, Ange Maguy, Stefano A De Simone, Michele Miragoli, Florian Jousset, Stephan Rohr
BACKGROUND: TGF-β1 (transforming growth factor-β1) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of cardiac myofibroblasts. It is still elusive, however, to which extent TGF-β1 alters the electrophysiological phenotype of myofibroblasts and cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte crosstalk observed in vitro. METHODS AND RESULTS: Patch-clamp recordings of cultured neonatal rat ventricular myofibroblasts revealed that TGF-β1, applied for 24 to 48 hours at clinically relevant concentrations (≤2...
May 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28497843/heart-failure-pilot-transcriptomic-analysis-of-cardiac-tissue-by-rna-sequencing
#16
Concetta Schiano, Valerio Costa, Marianna Aprile, Vincenzo Grimaldi, Ciro Maiello, Roberta Esposito, Andrea Soricelli, Vittorio Colantuoni, Francesco Donatelli, Alfredo Ciccodicola, Claudio Napoli
BACKGROUND: Despite left ventricular (LV) dysfunction contributing to mortality in chronic heart failure (HF), the molecular mechanisms of LV failure continues to remain poorly understood and myocardial biomarkers have yet to be identified. The aim of this pilot study was to investigate specific transcriptome changes occurring in cardiac tissues of patients with HF compared to healthy condition patients to improve diagnosis and possible treatment of affected subjects. METHODS: Unlike other studies, only dilated cardiomyopathy (DCM) (n = 2) and restrictive cardiomyopathy (RCM) (n = 2) patients who did not report family history of the disease were selected with the aim of obtaining a homogeneous population for the study...
May 12, 2017: Cardiology Journal
https://www.readbyqxmd.com/read/28487390/activation-of-the-amino-acid-response-pathway-blunts-the-effects-of-cardiac-stress
#17
Pu Qin, Pelin Arabacilar, Roberta E Bernard, Weike Bao, Alan R Olzinski, Yuanjun Guo, Hind Lal, Stephen H Eisennagel, Michael C Platchek, Wensheng Xie, Julius Del Rosario, Mohamad Nayal, Quinn Lu, Theresa Roethke, Christine G Schnackenberg, Fe Wright, Michael P Quaile, Wendy S Halsey, Ashley M Hughes, Ganesh M Sathe, George P Livi, Robert B Kirkpatrick, Xiaoyan A Qu, Deepak K Rajpal, Maria Faelth Savitski, Marcus Bantscheff, Gerard Joberty, Giovanna Bergamini, Thomas L Force, Gregory J Gatto, Erding Hu, Robert N Willette
BACKGROUND: The amino acid response (AAR) is an evolutionarily conserved protective mechanism activated by amino acid deficiency through a key kinase, general control nonderepressible 2. In addition to mobilizing amino acids, the AAR broadly affects gene and protein expression in a variety of pathways and elicits antifibrotic, autophagic, and anti-inflammatory activities. However, little is known regarding its role in cardiac stress. Our aim was to investigate the effects of halofuginone, a prolyl-tRNA synthetase inhibitor, on the AAR pathway in cardiac fibroblasts, cardiomyocytes, and in mouse models of cardiac stress and failure...
May 9, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28484475/de-novo-sequencing-and-transcriptome-analysis-reveal-key-genes-regulating-steroid-metabolism-in-leaves-roots-adventitious-roots-and-calli-of-periploca-sepium-bunge
#18
Jian Zhang, Xinglin Li, Fuping Lu, Shanying Wang, Yunhe An, Xiaoxing Su, Xiankuan Li, Lin Ma, Guangjian Han
Periploca sepium Bunge is a traditional medicinal plant, whose root bark is important for Chinese herbal medicine. Its major bioactive compounds are C21 steroids and periplocin, a kind of cardiac glycoside, which are derived from the steroid synthesis pathway. However, research on P. sepium genome or transcriptomes and their related genes has been lacking for a long time. In this study we estimated this species nuclear genome size at 170 Mb (using flow cytometry). Then, RNA sequencing of four different tissue samples of P...
2017: Frontiers in Plant Science
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
#19
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/28455512/systematic-identification-and-characterization-of-cardiac-long-intergenic-noncoding-rnas-in-zebrafish
#20
Lei Wang, Xiao Ma, Xiaolei Xu, Yuji Zhang
Long intergenic noncoding RNAs (lincRNAs) are increasingly recognized as potential key regulators of heart development and related diseases, but their identities and functions remain elusive. In this study, we sought to identify and characterize the cardiac lincRNA transcriptome in the experimentally accessible zebrafish model by integrating bioinformatics analysis with experimental validation. By conducting genome-wide RNA sequencing profiling of zebrafish embryonic hearts, adult hearts, and adult muscle, we generated a high-confidence set of 813 cardiac lincRNA transcripts, 423 of which are novel...
April 28, 2017: Scientific Reports
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