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https://www.readbyqxmd.com/read/28193895/p53-regulates-the-cardiac-transcriptome
#1
Tak W Mak, Ludger Hauck, Daniela Grothe, Filio Billia
The tumor suppressor Trp53 (p53) inhibits cell growth after acute stress by regulating gene transcription. The mammalian genome contains hundreds of p53-binding sites. However, whether p53 participates in the regulation of cardiac tissue homeostasis under normal conditions is not known. To examine the physiologic role of p53 in adult cardiomyocytes in vivo, Cre-loxP-mediated conditional gene targeting in adult mice was used. Genome-wide transcriptome analyses of conditional heart-specific p53 knockout mice were performed...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28167635/defined-engineered-human-myocardium-with-advanced-maturation-for-applications-in-heart-failure-modelling-and-repair
#2
Malte Tiburcy, James E Hudson, Paul Balfanz, Susanne F Schlick, Tim Meyer, Mei-Ling Chang Liao, Elif Levent, Farah Raad, Sebastian Zeidler, Edgar Wingender, Johannes Riegler, Mouer Wang, Joseph D Gold, Itzhak Kehat, Erich Wettwer, Ursula Ravens, Pieterjan Dierickx, Linda van Laake, Marie-José Goumans, Sara Khadjeh, Karl Toischer, Gerd Hasenfuss, Larry A Couture, Andreas Unger, Wolfgang A Linke, Toshiyuki Araki, Benjamin Neel, Gordon Keller, Lior Gepstein, Joseph C Wu, Wolfram-Hubertus Zimmermann
BACKGROUND: -Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modelling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) towards an adult phenotype under defined conditions. METHODS: -We systematically investigated cell composition, matrix and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions...
February 6, 2017: Circulation
https://www.readbyqxmd.com/read/28163252/the-legacy-pesticide-dieldrin-acts-as-a-teratogen-and-alters-the-expression-of-dopamine-transporter-and-dopamine-receptor-2a-in-zebrafish-danio-rerio-embryos
#3
Kathleena I Sarty, Andrew Cowie, Christopher J Martyniuk
Dieldrin (DLD) is a lipophilic pesticide that shows environmental persistence. The objectives were to determine the effects of DLD on GABAergic and dopaminergic systems in developing zebrafish. Both chorionated and dechorionated embryos (~24h post-hatch) were exposed to a single concentration of DLD (0.347-3470μM) for 48h. Following exposure, a subset of larvae was placed into clean water for 6days (i.e. depuration phase). Chorionated embryos showed <15% mortality while dechorionated embryos showed higher mortality (>30%), suggesting that the chorion protected the embryos...
February 3, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28158196/transcriptome-wide-co-expression-analysis-identifies-lrrc2-as-a-novel-mediator-of-mitochondrial-and-cardiac-function
#4
Chris McDermott-Roe, Marion Leleu, Glenn C Rowe, Oleg Palygin, John D Bukowy, Judy Kuo, Monika Rech, Steffie Hermans-Beijnsberger, Sebastian Schaefer, Eleonora Adami, Esther E Creemers, Matthias Heinig, Blanche Schroen, Zoltan Arany, Enrico Petretto, Aron M Geurts
Mitochondrial dysfunction contributes to myriad monogenic and complex pathologies. To understand the underlying mechanisms, it is essential to define the full complement of proteins that modulate mitochondrial function. To identify such proteins, we performed a meta-analysis of publicly available gene expression data. Gene co-expression analysis of a large and heterogeneous compendium of microarray data nominated a sub-population of transcripts that whilst highly correlated with known mitochondrial protein-encoding transcripts (MPETs), are not themselves recognized as generating proteins either localized to the mitochondrion or pertinent to functions therein...
2017: PloS One
https://www.readbyqxmd.com/read/28152015/identification-of-the-early-and-late-responder-genes-during-the-generation-of-induced-pluripotent-stem-cells-from-mouse-fibroblasts
#5
Jihwan Park, Yoo-Wook Kwon, Seokjin Ham, Chang-Pyo Hong, Seonghye Seo, Moon Kyung Choe, So-I Shin, Choon-Soo Lee, Hyo-Soo Kim, Tae-Young Roh
BACKGROUND: The generation of induced pluripotent stem cell (iPSC), a substitute for embryonic stem cell (ESC), requires the proper orchestration of a transcription program at the chromatin level. Our recent approach for the induction of pluripotent stem cells from fibroblasts using protein extracts from mouse ESCs could overcome the potential tumorigenicity risks associated with random retroviral integration. Here, we examine the epigenetic modifications and the transcriptome of two types of iPSC and of partially reprogrammed iPSCs (iPSCp) generated independently from adult cardiac and skin fibroblasts to assess any perturbations of the transcription program during reprogramming...
2017: PloS One
https://www.readbyqxmd.com/read/28147324/identification-of-novel-biomarkers-for-prediction-of-neurological-prognosis-following-cardiac-arrest
#6
Jung Woo Eun, Hee Doo Yang, Soo Hyun Kim, Sungyoup Hong, Kyu Nam Park, Suk Woo Nam, Sikyoung Jeong
BACKGROUND: Early prognostication of neurological outcome in comatose patients after cardiac arrest (CA) is important for devising patient treatment strategies. However, there is still a lack of sensitive and specific biomarkers for easy identification of these patients. We evaluated whether molecular signatures from blood of CA patients might help to improve the prediction of neurological outcome. METHODS: We examined 22 comatose patients resuscitated after CA and obtained peripheral blood samples 48 hours after CA...
January 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28134617/modeling-susceptibility-to-drug-induced-long-qt-with-a-panel-of-subject-specific-induced-pluripotent-stem-cells
#7
Francesca Stillitano, Jens Hansen, Chi-Wing Kong, Ioannis Karakikes, Christian Funck-Brentano, Lin Geng, Stuart Scott, Stephan Reynier, Ma Wu, Yannick Valogne, Carole Desseaux, Joe-Elie Salem, Dorota Jeziorowska, Noël Zahr, Ronald Li, Ravi Iyengar, Roger J Hajjar, Jean-Sébastien Hulot
A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol...
January 30, 2017: ELife
https://www.readbyqxmd.com/read/28132643/comparative-transcriptomics-of-elasmobranchs-and-teleosts-highlight-important-processes-in-adaptive-immunity-and-regional-endothermy
#8
Nicholas J Marra, Vincent P Richards, Angela Early, Steve M Bogdanowicz, Paulina D Pavinski Bitar, Michael J Stanhope, Mahmood S Shivji
BACKGROUND: Comparative genomic and/or transcriptomic analyses involving elasmobranchs remain limited, with genome level comparisons of the elasmobranch immune system to that of higher vertebrates, non-existent. This paper reports a comparative RNA-seq analysis of heart tissue from seven species, including four elasmobranchs and three teleosts, focusing on immunity, but concomitantly seeking to identify genetic similarities shared by the two lamnid sharks and the single billfish in our study, which could be linked to convergent evolution of regional endothermy...
January 30, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28104771/circulating-noncoding-rnas-as-biomarkers-of-cardiovascular-disease-and-injury
#9
REVIEW
Janika Viereck, Thomas Thum
The discovery of thousands of noncoding RNAs (ncRNAs) has expanded our view on mammalian genomes and transcriptomes, as well as their organization and regulation. Accumulating evidence on aberrantly regulated ncRNAs, including short microRNAs, long ncRNAs and circular RNAs, across various heart diseases indicates that ncRNAs are critical contributors to cardiovascular pathophysiology. In addition, ncRNAs are released into the circulation where they are present in concentration levels that differ between healthy subjects and diseased patients...
January 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28101782/the-antineoplastic-drug-trastuzumab-dysregulates-metabolism-in-ipsc-derived-cardiomyocytes
#10
Brian M Necela, Bianca C Axenfeld, Daniel J Serie, Jennifer M Kachergus, Edith A Perez, E Aubrey Thompson, Nadine Norton
BACKGROUND: The targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC-derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 h and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28090760/expression-patterns-of-cardiac-aging-in-drosophila
#11
Leah Cannon, Alexander C Zambon, Anthony Cammarato, Zhi Zhang, Georg Vogler, Matthew Munoz, Erika Taylor, Jérôme Cartry, Sanford I Bernstein, Simon Melov, Rolf Bodmer
Aging causes cardiac dysfunction, often leading to heart failure and death. The molecular basis of age-associated changes in cardiac structure and function is largely unknown. The fruit fly, Drosophila melanogaster, is well-suited to investigate the genetics of cardiac aging. Flies age rapidly over the course of weeks, benefit from many tools to easily manipulate their genome, and their heart has significant genetic and phenotypic similarities to the human heart. Here, we performed a cardiac-specific gene expression study on aging Drosophila and carried out a comparative meta-analysis with published rodent data...
February 2017: Aging Cell
https://www.readbyqxmd.com/read/28073833/exosomal-mir-142-3p-is-increased-during-cardiac-allograft-rejection-and-augments-vascular-permeability-through-down-regulation-of-endothelial-rab11fip2-expression
#12
Ihdina Sukma Dewi, Selvi Celik, Anna Karlsson, Zsuzsanna Hollander, Karen Lam, Janet-Wilson McManus, Scott Tebbutt, Raymond Ng, Paul Keown, Robert McMaster, Bruce McManus, Jenny Öhman, Olof Gidlöf
AIMS: Exosome-mediated microRNA transfer is a recently discovered mode of cell-to-cell communication, in which microRNAs act as paracrine molecules, exerting their regulatory effects in recipient cells. T cells and endothelial cells are two main players in the mechanism of acute cellular cardiac rejection. The aim of this study was to investigate the role of exosomal microRNAs in the crosstalk between T cells and endothelial cells and its implications for the molecular mechanisms that drive acute cellular rejection in heart transplantation...
January 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28064149/emerging-roles-for-rna-binding-proteins-as-effectors-and-regulators-of-cardiovascular-disease
#13
REVIEW
Ruben G de Bruin, Ton J Rabelink, Anton Jan van Zonneveld, Eric P van der Veer
The cardiovascular system comprises multiple cell types that possess the capacity to modulate their phenotype in response to acute or chronic injury. Transcriptional and post-transcriptional mechanisms play a key role in the regulation of remodelling and regenerative responses to damaged cardiovascular tissues. Simultaneously, insufficient regulation of cellular phenotype is tightly coupled with the persistence and exacerbation of cardiovascular disease. Recently, RNA-binding proteins such as Quaking, HuR, Muscleblind, and SRSF1 have emerged as pivotal regulators of these functional adaptations in the cardiovascular system by guiding a wide-ranging number of post-transcriptional events that dramatically impact RNA fate, including alternative splicing, stability, localization and translation...
January 6, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28038934/emerging-cardiac-non-coding-landscape-the-importance-of-meta-analysis
#14
REVIEW
K Shanmugha Rajan, Subbiah Ramasamy, J N George-William, Jeyaprakash Rajendhran
The invention of transcriptome-wide deep sequencing technology has fundamentally changed our understanding of the complex networks that mediate cardiac functions. Since its inception, researchers have uncovered various novel pathways and transcripts that could be one day used for therapeutics and diagnostics. The characterization of various non-protein coding RNAs (ncRNAs) has aided the study of cardiac manifestation in more detail. Although numerous studies have unearthed the importance of miRNA and lncRNA, the existence and importance of other ncRNAs have been neglected due to their unusual behaviors and outdated ideologies...
February 2017: Biochimie
https://www.readbyqxmd.com/read/28007739/ischemic-preconditioning-confers-epigenetic-repression-of-mtor-and-induction-of-autophagy-through-g9a-dependent-h3k9-dimethylation
#15
Olof Gidlöf, Andrea L Johnstone, Kerstin Bader, Bohdan B Khomtchouk, Jiaqi J O'Reilly, Selvi Celik, Derek J Van Booven, Claes Wahlestedt, Bernhard Metzler, David Erlinge
BACKGROUND: Ischemic preconditioning (IPC) protects the heart from prolonged ischemic insult and reperfusion injury through a poorly understood mechanism. Post-translational modifications of histone residues can confer rapid and drastic switches in gene expression in response to various stimuli, including ischemia. The aim of this study was to investigate the effect of histone methylation in the response to cardiac ischemic preconditioning. METHODS AND RESULTS: We used cardiac biopsies from mice subjected to IPC to quantify global levels of 3 of the most well-studied histone methylation marks (H3K9me2, H3K27me3, and H3K4me3) with Western blot and found that H3K9me2 levels were significantly increased in the area at risk compared to remote myocardium...
December 22, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27927713/high-fibre-diet-and-acetate-supplementation-change-the-gut-microbiota-and-prevent-the-development-of-hypertension-and-heart-failure-in-doca-salt-hypertensive-mice
#16
Francine Z Marques, Erin M Nelson, Po-Yin Chu, Duncan Horlock, April Fiedler, Mark Ziemann, Jian K Tan, Sanjaya Kuruppu, Niwanthi W Rajapakse, Assam El-Osta, Charles R Mackay, David M Kaye
BACKGROUND: -Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here we evaluated the effect of a high fibre diet and supplementation with the short-chain fatty acid (SFCA) acetate on the gut microbiota and the prevention of cardiovascular disease. METHODS: -Gut microbiome, cardiorenal structure/function and blood pressure were examined in sham and mineralocorticoid-excess treated mice with a control diet, high fibre diet or acetate supplementation...
December 7, 2016: Circulation
https://www.readbyqxmd.com/read/27893464/the-h3k9-dimethyltransferases-ehmt1-2-protect-against-pathological-cardiac-hypertrophy
#17
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/27866946/systems-genetics-approach-identifies-gene-pathways-and-adamts2-as-drivers-of-isoproterenol-induced-cardiac-hypertrophy-and-cardiomyopathy-in-mice
#18
Christoph D Rau, Milagros C Romay, Mary Tuteryan, Jessica J-C Wang, Marc Santolini, Shuxun Ren, Alain Karma, James N Weiss, Yibin Wang, Aldons J Lusis
We previously reported a genetic analysis of heart failure traits in a population of inbred mouse strains treated with isoproterenol to mimic catecholamine-driven cardiac hypertrophy. Here, we apply a co-expression network algorithm, wMICA, to perform a systems-level analysis of left ventricular transcriptomes from these mice. We describe the features of the overall network but focus on a module identified in treated hearts that is strongly related to cardiac hypertrophy and pathological remodeling. Using the causal modeling algorithm NEO, we identified the gene Adamts2 as a putative regulator of this module and validated the predictive value of NEO using small interfering RNA-mediated knockdown in neonatal rat ventricular myocytes...
January 25, 2017: Cell Systems
https://www.readbyqxmd.com/read/27834691/zebrafish-model-for-functional-screening-of-flow-responsive-genes
#19
Jovana Serbanovic-Canic, Amalia de Luca, Christina Warboys, Pedro F Ferreira, Le A Luong, Sarah Hsiao, Ismael Gauci, Marwa Mahmoud, Shuang Feng, Celine Souilhol, Neil Bowden, John-Paul Ashton, Henning Walczak, David Firmin, Rob Krams, Justin C Mason, Dorian O Haskard, Spencer Sherwin, Victoria Ridger, Timothy J A Chico, Paul C Evans
OBJECTIVE: Atherosclerosis is initiated at branches and bends of arteries exposed to disturbed blood flow that generates low shear stress. This mechanical environment promotes lesions by inducing endothelial cell (EC) apoptosis and dysfunction via mechanisms that are incompletely understood. Although transcriptome-based studies have identified multiple shear-responsive genes, most of them have an unknown function. To address this, we investigated whether zebrafish embryos can be used for functional screening of mechanosensitive genes that regulate EC apoptosis in mammalian arteries...
January 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27832192/transcriptome-dynamics-and-potential-roles-of-sox6-in-the-postnatal-heart
#20
Chung-Il An, Yasunori Ichihashi, Jie Peng, Neelima R Sinha, Nobuko Hagiwara
The postnatal heart undergoes highly coordinated developmental processes culminating in the complex physiologic properties of the adult heart. The molecular mechanisms of postnatal heart development remain largely unexplored despite their important clinical implications. To gain an integrated view of the dynamic changes in gene expression during postnatal heart development at the organ level, time-series transcriptome analyses of the postnatal hearts of neonatal through adult mice (P1, P7, P14, P30, and P60) were performed using a newly developed bioinformatics pipeline...
2016: PloS One
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