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https://www.readbyqxmd.com/read/29452236/cardiac-and-placental-mitochondrial-characterization-in-a-rabbit-model-of-intrauterine-growth-restriction
#1
M Guitart-Mampel, A Gonzalez-Tendero, S Niñerola, C Morén, M Catalán-Garcia, I González-Casacuberta, D L Juárez-Flores, O Ugarteburu, L Matalonga, M V Cascajo, F Tort, A Cortés, E Tobias, J C Milisenda, J M Grau, F Crispi, E Gratacós, G Garrabou, F Cardellach
BACKGROUND: Intrauterine growth restriction (IUGR) is associated with cardiovascular remodeling persisting into adulthood. Mitochondrial bioenergetics, essential for embryonic development and cardiovascular function, are regulated by nuclear effectors as sirtuins. A rabbit model of IUGR and cardiovascular remodeling was generated, in which heart mitochondrial alterations were observed by microscopic and transcriptomic analysis. We aimed to evaluate if such alterations are translated at a functional mitochondrial level to establish the etiopathology and potential therapeutic targets for this obstetric complication...
February 13, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29449571/an-in-silico-argument-for-mitochondrial-microrna-as-a-determinant-of-primary-non-function-in-liver-transplantation
#2
Shirin Elizabeth Khorsandi, Siamak Salehi, Miriam Cortes, Hector Vilca-Melendez, Krishna Menon, Parthi Srinivasan, Andreas Prachalias, Wayel Jassem, Nigel Heaton
Mitochondria have their own genomic, transcriptomic and proteomic machinery but are unable to be autonomous, needing both nuclear and mitochondrial genomes. The aim of this work was to use computational biology to explore the involvement of Mitochondrial microRNAs (MitomiRs) and their interactions with the mitochondrial proteome in a clinical model of primary non function (PNF) of the donor after cardiac death (DCD) liver. Archival array data on the differential expression of miRNA in DCD PNF was re-analyzed using a number of publically available computational algorithms...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29440116/improving-interpretation-of-cardiac-phenotypes-and-enhancing-discovery-with-expanded-knowledge-in-the-gene-ontology
#3
Ruth C Lovering, Paola Roncaglia, Douglas G Howe, Stanley J F Laulederkind, Varsha K Khodiyar, Tanya Z Berardini, Susan Tweedie, Rebecca E Foulger, David Osumi-Sutherland, Nancy H Campbell, Rachael P Huntley, Philippa J Talmud, Judith A Blake, Ross Breckenridge, Paul R Riley, Pier D Lambiase, Perry M Elliott, Lucie Clapp, Andrew Tinker, David P Hill
BACKGROUND: A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. METHODS AND RESULTS: In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology...
February 2018: Circ Genom Precis Med
https://www.readbyqxmd.com/read/29421235/analysis-of-rat-cardiac-myocytes-and-fibroblasts-identifies-combinatorial-enhancer-organization-and-transcription-factor-families
#4
Tal Golan-Lagziel, Yair E Lewis, Omer Shkedi, Guy Douvdevany, Lilac H Caspi, Izhak Kehat
Cardiac fibroblasts play key roles in both health and disease. Their regulatory elements, transcription factors (TFs), and mechanisms of expression control have not been fully elucidated. We used a differential open chromatin approach, coupled with active enhancer mark, transcriptomic, and computational TFs binding analysis to map cell-type-specific active enhancers in cardiac fibroblasts and cardiomyocytes, and outline the TFs families that control them. This approach was validated by its ability to uncover the known cardiomyocyte TF biology in an unbiased manner, and was then applied to cardiac fibroblasts...
February 5, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29400650/spatially-resolved-rna-sequencing-of-the-embryonic-heart-identifies-a-role-for-wnt-%C3%AE-catenin-signaling-in-autonomic-control-of-heart-rate
#5
Silja Barbara Burkhard, Jeroen Bakkers
Development of specialized cells and structures in the heart is regulated by spatially-restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue-sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments...
February 5, 2018: ELife
https://www.readbyqxmd.com/read/29398480/comparison-of-non-human-primate-versus-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-for-treatment-of-myocardial-infarction
#6
Xin Zhao, Haodong Chen, Dan Xiao, Huaxiao Yang, Ilanit Itzhaki, Xulei Qin, Tony Chour, Aitor Aguirre, Kim Lehmann, Youngkyun Kim, Praveen Shukla, Alexandra Holmström, Joe Z Zhang, Yan Zhuge, Babacar C Ndoye, Mingtao Zhao, Evgenios Neofytou, Wolfram-Hubertus Zimmermann, Mohit Jain, Joseph C Wu
Non-human primates (NHPs) can serve as a human-like model to study cell therapy using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, whether the efficacy of NHP and human iPSC-CMs is mechanistically similar remains unknown. To examine this, RNU rats received intramyocardial injection of 1 × 10 7 NHP or human iPSC-CMs or the same number of respective fibroblasts or PBS control (n = 9-14/group) at 4 days after 60-min coronary artery occlusion-reperfusion. Cardiac function and left ventricular remodeling were similarly improved in both iPSC-CM-treated groups...
February 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29394407/a-context-specific-cardiac-%C3%AE-catenin-and-gata4-interaction-influences-tcf7l2-occupancy-and-remodels-chromatin-driving-disease-progression-in-the-adult-heart
#7
Lavanya M Iyer, Sankari Nagarajan, Monique Woelfer, Eric Schoger, Sara Khadjeh, Maria Patapia Zafiriou, Vijayalakshmi Kari, Jonas Herting, Sze Ting Pang, Tobias Weber, Franziska S Rathjens, Thomas H Fischer, Karl Toischer, Gerd Hasenfuss, Claudia Noack, Steven A Johnsen, Laura C Zelarayán
Chromatin remodelling precedes transcriptional and structural changes in heart failure. A body of work suggests roles for the developmental Wnt signalling pathway in cardiac remodelling. Hitherto, there is no evidence supporting a direct role of Wnt nuclear components in regulating chromatin landscapes in this process. We show that transcriptionally active, nuclear, phosphorylated(p)Ser675-β-catenin and TCF7L2 are upregulated in diseased murine and human cardiac ventricles. We report that inducible cardiomyocytes (CM)-specific pSer675-β-catenin accumulation mimics the disease situation by triggering TCF7L2 expression...
January 31, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29386203/single-cell-sequencing-of-the-healthy-and-diseased-heart-reveals-ckap4-as-a-new-modulator-of-fibroblasts-activation
#8
Monika M Gladka, Bas Molenaar, Hesther de Ruiter, Stefan van der Elst, Hoyee Tsui, Danielle Versteeg, Grègory P A Lacraz, Manon M H Huibers, Alexander van Oudenaarden, Eva van Rooij
Background -Genome-wide transcriptome analysis has greatly advanced our understanding of the regulatory networks underlying basic cardiac biology and mechanisms driving disease. However, so far, the resolution of studying gene expression patterns in the adult heart has been limited to the level of extracts from whole tissues. The use of tissue homogenates inherently causes the loss of any information on cellular origin or cell type-specific changes in gene expression. Recent developments in RNA amplification strategies provide a unique opportunity to use small amounts of input RNA for genome-wide sequencing of single cells...
January 31, 2018: Circulation
https://www.readbyqxmd.com/read/29377178/distinct-patterns-of-gene-expression-in-human-cardiac-fibroblasts-exposed-to-rapamycin-treatment-or-methionine-restriction
#9
Ashley Azar, Ibiyonu Lawrence, Sebastian Jofre, Joshua Mell, Christian Sell
Both methionine restriction and rapamycin treatment are robust longevity-enhancing regimens for which the mechanisms remain unclear. Cellular senescence is a major contributor to the aging process, and we find that both the methionine and rapamycin regimens delay or prevent activation of the senescence program in human cells. Using a transcriptome-wide analysis, we examined the impact of methionine restriction and rapamycin treatment on senescence-associated gene expression in human cardiac fibroblasts. Our findings have been integrated into gene expression data sets from human lung and skin fibroblasts during senescence...
January 28, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29374152/distinct-epigenetic-programs-regulate-cardiac-myocyte-development-and-disease-in-the-human-heart-in-vivo
#10
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/29373717/integrated-transcriptomic-and-regulatory-network-analyses-identify-microrna-200c-as-a-novel-repressor-of-human-pluripotent-stem-cell-derived-cardiomyocyte-differentiation-and-maturation
#11
Ellen Ngar Yun Poon, Baixia Hao, Daogang Guan, Mulin Jun Li, Jun Lu, Yong Yang, Binbin Wu, Stanley Chun Ming Wu, Sarah E Webb, Yan Liang, Andrew L Miller, Xiaoqiang Yao, Junwen Wang, Bin Yan, Kenneth R Boheler
Aims: MicroRNAs (miRNAs) are crucial for the post-transcriptional control of protein-encoding genes, and together with transcription factors (TFs) regulate gene expression; however, the regulatory activities of miRNAs during cardiac development are only partially understood. In this study, we tested the hypothesis that integrative computational approaches could identify miRNAs that experimentally could be shown to regulate cardiomyogenesis. Methods and results: We integrated expression profiles with bioinformatics analyses of miRNA and TF regulatory programs to identify candidate miRNAs involved with cardiac development...
January 24, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29352247/high-content-analysis-identifies-unique-morphological-features-of-reprogrammed-cardiomyocytes
#12
Matthew D Sutcliffe, Philip M Tan, Antonio Fernandez-Perez, Young-Jae Nam, Nikhil V Munshi, Jeffrey J Saucerman
Direct reprogramming of fibroblasts into cardiomyocytes is a promising approach for cardiac regeneration but still faces challenges in efficiently generating mature cardiomyocytes. Systematic optimization of reprogramming protocols requires scalable, objective methods to assess cellular phenotype beyond what is captured by transcriptional signatures alone. To address this question, we automatically segmented reprogrammed cardiomyocytes from immunofluorescence images and analyzed cell morphology. We also introduce a method to quantify sarcomere structure using Haralick texture features, called SarcOmere Texture Analysis (SOTA)...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351515/understanding-key-mechanisms-of-exercise-induced-cardiac-protection-to-mitigate-disease-current-knowledge-and-emerging-concepts
#13
Bianca C Bernardo, Jenny Y Y Ooi, Kate L Weeks, Natalie L Patterson, Julie R McMullen
The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29348408/nipbl-haploinsufficiency-reveals-a-constellation-of-transcriptome-disruptions-in-the-pluripotent-and-cardiac-states
#14
Jason A Mills, Pamela S Herrera, Maninder Kaur, Lanfranco Leo, Deborah McEldrew, Jesus A Tintos-Hernandez, Ramakrishnan Rajagopalan, Alyssa Gagne, Zhe Zhang, Xilma R Ortiz-Gonzalez, Ian D Krantz
Cornelia de Lange syndrome (CdLS) is a complex disorder with multiple structural and developmental defects caused by mutations in structural and regulatory proteins involved in the cohesin complex. NIPBL, a cohesin regulatory protein, has been identified as a critical protein responsible for the orchestration of transcriptomic regulatory networks necessary for embryonic development. Mutations in NIPBL are responsible for the majority of cases of CdLS. Through RNA-sequencing of human induced pluripotent stem cells and in vitro-derived cardiomyocytes, we identified hundreds of mRNAs, pseudogenes, and non-coding RNAs with altered expression in NIPBL+/- patient-derived cells...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348261/complement-receptor-c5ar1-plays-an-evolutionarily-conserved-role-in-successful-cardiac-regeneration
#15
Niranjana Natarajan, Yamen Abbas, Donald M Bryant, Juan Manuel Gonzalez-Rosa, Michka Sharpe, Aysu Uygur, Lucas H Cocco-Delgado, Nhi Ngoc Ho, Norma P Gerard, Craig J Gerard, Calum A Macrae, Caroline E Burns, C Geoffrey Burns, Jessica L Whited, Richard T Lee
Background -Defining conserved molecular pathways in animal models of successful cardiac regeneration could yield insight into why adult mammals have inadequate cardiac regeneration after injury. Insight into the transcriptomic landscape of early cardiac regeneration from model organisms will shed light on evolutionarily conserved pathways in successful cardiac regeneration. Methods -Here we describe a cross-species transcriptomic screen in three model organisms for cardiac regeneration -axolotl, neonatal mice and zebrafish...
January 18, 2018: Circulation
https://www.readbyqxmd.com/read/29336212/simulated-microgravity-impairs-cardiac-autonomic-neurogenesis-from-neural-crest-cells
#16
Konstantinos E Hatzistergos, Zhijie Jiang, Krystalenia Valasaki, Lauro M Takeuchi, Wayne Balkan, Preethi Atluri, Dieter Saur, Barbara Seidler, Nicholas Tsinoremas, Darcy DiFede, Joshua M Hare
Microgravity-induced alterations in the autonomic nervous system (ANS) contribute to derangements in both the mechanical and electrophysiologic function of the cardiovascular system, leading to severe symptoms in humans following space travel. Because the ANS forms embryonically from neural crest progenitors (NCs), we hypothesized that microgravity can impair NC derived cardiac structures. Accordingly, we conducted in vitro simulated microgravity experiments employing NC genetic lineage-tracing in mice with cKitCreERT2/+, Isl1nLacZ and Wnt1-Cre reporter alleles...
January 16, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29321036/maternal-engineered-nanomaterial-inhalation-during-gestation-alters-the-fetal-transcriptome
#17
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/29311597/putative-functional-genes-in-idiopathic-dilated-cardiomyopathy
#18
Nishanth Ulhas Nair, Avinash Das, Uri Amit, Welles Robinson, Seung Gu Park, Mahashweta Basu, Alex Lugo, Jonathan Leor, Eytan Ruppin, Sridhar Hannenhalli
Idiopathic dilated cardiomyopathy (DCM) is a complex disorder with a genetic and an environmental component involving multiple genes, many of which are yet to be discovered. We integrate genetic, epigenetic, transcriptomic, phenotypic, and evolutionary features into a method - Hridaya, to infer putative functional genes underlying DCM in a genome-wide fashion, using 213 human heart genomes and transcriptomes. Many genes identified by Hridaya are experimentally shown to cause cardiac complications. We validate the top predicted genes, via five different genome-wide analyses: First, the predicted genes are associated with cardiovascular functions...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29301788/cardiac-endothelial-cell-transcriptome
#19
Achim Lother, Stella Bergemann, Lisa Deng, Martin Moser, Christoph Bode, Lutz Hein
OBJECTIVE: Endothelial cells (ECs) are a highly specialized cell type with marked diversity between different organs or vascular beds. Cardiac ECs are an important player in cardiac physiology and pathophysiology but are not sufficiently characterized yet. Thus, the aim of the present study was to analyze the cardiac EC transcriptome. APPROACH AND RESULTS: We applied fluorescence-assisted cell sorting to isolate pure ECs from adult mouse hearts. RNAseq revealed 1288 genes predominantly expressed in cardiac ECs versus heart tissue including several transcription factors...
January 4, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29288185/cohort-profile-the-emory-cardiovascular-biobank-emcab
#20
Yi-An Ko, Salim Hayek, Pratik Sandesara, Ayman Samman Tahhan, Arshed Quyyumi
PURPOSE: The Emory Cardiovascular Biobank (EmCAB) is an ongoing prospective registry of patients undergoing cardiac catheterisation, which was established to identify novel factors associated with the pathobiological process and treatment of cardiovascular disease. PARTICIPANTS: Individuals aged 18 years and older undergoing cardiac catheterisation at three Emory Healthcare sites in Atlanta are asked to participate in this prospective registry. Around 95% agree to participate...
December 29, 2017: BMJ Open
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