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Transcriptome cardiac

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https://www.readbyqxmd.com/read/29036603/identification-of-optimal-reference-genes-for-transcriptomic-analyses-in-normal-and-diseased-human-heart
#1
Cristina E Molina, Eric Jacquet, Prishila Ponien, Christian Muñoz-Guijosa, Istvan Baczkó, Lars S Maier, Patrick Donzeau-Gouge, Dobromir Dobrev, Rodolphe Fischmeister, Anne Garnier
Aims: Quantitative real-time RT-PCR (RT-qPCR) has become the method of choice for mRNA quantification, but requires an accurate normalization based on the use of reference genes showing invariant expression across various pathological conditions. Only few data exist on appropriate reference genes for the human heart. The objective of this study was to determine a set of suitable reference genes in human atrial and ventricular tissues, from right and left cavities in control and in cardiac diseases...
September 22, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29030402/transcriptome-and-functional-profile-of-cardiac-myocytes-is-influenced-by-biological-sex
#2
Christa L Trexler, Aaron T Odell, Mark Y Jeong, Robin D Dowell, Leslie A Leinwand
BACKGROUND: Although cardiovascular disease is the primary killer of women in the United States, women and female animals have traditionally been omitted from research studies. In reports that do include both sexes, significant sexual dimorphisms have been demonstrated in development, presentation, and outcome of cardiovascular disease. However, there is little understanding of the mechanisms underlying these observations. A more thorough understanding of sex-specific cardiovascular differences both at baseline and in disease is required to effectively consider and treat all patients with cardiovascular disease...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29026152/genetic-and-epigenetic-profiling-reveals-ezh2-mediated-down-regulation-of-oct-4-involves-nr2f2-during-cardiac-differentiation-of-human-embryonic-stem-cells
#3
Varsha Pursani, Prasad Pethe, Mohsin Bashir, Prabha Sampath, Vivek Tanavde, Deepa Bhartiya
Human embryonic (hES) stem cells are widely used as an in vitro model to understand global genetic and epigenetic changes that occur during early embryonic development. In-house derived hES cells (KIND1) were subjected to directed differentiation into cardiovascular progenitors (D12) and beating cardiomyocytes (D20). Transcriptome profiling of undifferentiated (D0) and differentiated (D12 and 20) cells was undertaken by microarray analysis. ChIP and sequential ChIP were employed to study role of transcription factor NR2F2 during hES cells differentiation...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29021611/spatial-detection-of-fetal-marker-genes-expressed-at-low-level-in-adult-human-heart-tissue
#4
Michaela Asp, Fredrik Salmén, Patrik L Ståhl, Sanja Vickovic, Ulrika Felldin, Marie Löfling, José Fernandez Navarro, Jonas Maaskola, Maria J Eriksson, Bengt Persson, Matthias Corbascio, Hans Persson, Cecilia Linde, Joakim Lundeberg
Heart failure is a major health problem linked to poor quality of life and high mortality rates. Hence, novel biomarkers, such as fetal marker genes with low expression levels, could potentially differentiate disease states in order to improve therapy. In many studies on heart failure, cardiac biopsies have been analyzed as uniform pieces of tissue with bulk techniques, but this homogenization approach can mask medically relevant phenotypes occurring only in isolated parts of the tissue. This study examines such spatial variations within and between regions of cardiac biopsies...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29020403/cardiac-and-systemic-rejuvenation-after-cardiosphere-derived-cell-therapy-in-senescent-rats
#5
Lilian Grigorian-Shamagian, Weixin Liu, Soraya Fereydooni, Ryan C Middleton, Jackelyn Valle, Jae Hyung Cho, Eduardo Marbán
Aim: The aim is to assess the effects of CDCs on heart structure, function, gene expression, and systemic parameters in aged rats. Diastolic dysfunction is characteristic of aged hearts. Cardiosphere-derived cell (CDC) therapy has exhibited several favourable effects on heart structure and function in humans and in preclinical models; however, the effects of CDCs on aging have not been evaluated. Methods and Results: We compared intra-cardiac injections of neonatal rat CDCs to vehicle (phosphate-buffered saline, PBS) in 21...
August 14, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28992430/human-induced-pluripotent-stem-cell-hipsc-derived-cells-to-assess-drug-cardiotoxicity-opportunities-and-problems
#6
Tarek Magdy, Adam J T Schuldt, Joseph C Wu, Daniel Bernstein, Paul W Burridge
Billions of US dollars are invested every year by the pharmaceutical industry in drug development, with the aim of introducing new drugs that are effective and have minimal side effects. Thirty percent of in-pipeline drugs are excluded in an early phase of preclinical and clinical screening owing to cardiovascular safety concerns, and several lead molecules that pass the early safety screening make it to market but are later withdrawn owing to severe cardiac side effects. Although the current drug safety screening methodologies can identify some cardiotoxic drug candidates, they cannot accurately represent the human heart in many aspects, including genomics, transcriptomics, and patient- or population-specific cardiotoxicity...
October 6, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28954220/comparative-gene-expression-analyses-reveal-distinct-molecular-signatures-between-differentially-reprogrammed-cardiomyocytes
#7
Yang Zhou, Li Wang, Ziqing Liu, Sahar Alimohamadi, Chaoying Yin, Jiandong Liu, Li Qian
Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) or directly reprogrammed from non-myocytes (induced cardiomyocytes [iCMs]) are promising sources for heart regeneration or disease modeling. However, the similarities and differences between iPSC-CMs and iCMs are still unknown. Here, we performed transcriptome analyses of beating iPSC-CMs and iCMs generated from cardiac fibroblasts (CFs) of the same origin. Although both iPSC-CMs and iCMs establish CM-like molecular features globally, iPSC-CMs exhibit a relatively hyperdynamic epigenetic status, whereas iCMs exhibit a maturation status that more closely resembles that of adult CMs...
September 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/28947747/a-whole-blood-molecular-signature-for-acute-myocardial-infarction
#8
Evan D Muse, Eric R Kramer, Haiying Wang, Paddy Barrett, Fereshteh Parviz, Mark A Novotny, Roger S Lasken, Timothy A Jatkoe, Glenn Oliveira, Hongfan Peng, Jerry Lu, Mark C Connelly, Kurt Schilling, Chandra Rao, Ali Torkamani, Eric J Topol
Chest pain is a leading reason patients seek medical evaluation. While assays to detect myocyte death are used to diagnose a heart attack (acute myocardial infarction, AMI), there is no biomarker to indicate an impending cardiac event. Transcriptional patterns present in circulating endothelial cells (CEC) may provide a window into the plaque rupture process and identify a proximal biomarker for AMI. Thus, we aimed to identify a transcriptomic signature of AMI present in whole blood, but derived from CECs. Candidate genes indicative of AMI were nominated from microarray of enriched CEC samples, and then verified for detectability and predictive potential via qPCR in whole blood...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28942281/antihypertrophic-effects-of-small-molecules-that-maintain-mitochondrial-atp-levels-under-hypoxia
#9
Hiroaki Nagai, Tomoko Satomi, Akiko Abiru, Kazumasa Miyamoto, Koji Nagasawa, Minoru Maruyama, Satoshi Yamamoto, Kuniko Kikuchi, Hiromitsu Fuse, Masakuni Noda, Yoshiyuki Tsujihata
Since impaired mitochondrial ATP production in cardiomyocytes is thought to lead to heart failure, a drug that protects mitochondria and improves ATP production under disease conditions would be an attractive treatment option. In this study, we identified small-molecule drugs, including the anti-parasitic agent, ivermectin, that maintain mitochondrial ATP levels under hypoxia in cardiomyocytes. Mechanistically, transcriptomic analysis and gene silencing experiments revealed that ivermectin increased mitochondrial ATP production by inducing Cox6a2, a subunit of the mitochondrial respiratory chain...
September 19, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28941705/severe-dcm-phenotype-of-patient-harboring-rbm20-mutation-s635a-can-be-modeled-by-patient-specific-induced-pluripotent-stem-cell-derived-cardiomyocytes
#10
Katrin Streckfuss-Bömeke, Malte Tiburcy, Andrey Fomin, Xiaojing Luo, Wener Li, Claudia Fischer, Cemil Özcelik, Andreas Perrot, Samuel Sossalla, Jan Haas, Ramon Oliveira Vidal, Sabine Rebs, Sara Khadjeh, Benjamin Meder, Stefan Bonn, Wolfgang A Linke, Wolfram-Hubertus Zimmermann, Gerd Hasenfuss, Kaomei Guan
The ability to generate patient-specific induced pluripotent stem cells (iPSCs) provides a unique opportunity for modeling heart disease in vitro. In this study, we generated iPSCs from a patient with dilated cardiomyopathy (DCM) caused by a missense mutation S635A in RNA-binding motif protein 20 (RBM20) and investigated the functionality and cell biology of cardiomyocytes (CMs) derived from patient-specific iPSCs (RBM20-iPSCs). The RBM20-iPSC-CMs showed abnormal distribution of sarcomeric α-actinin and defective calcium handling compared to control-iPSC-CMs, suggesting disorganized myofilament structure and altered calcium machinery in CMs of the RBM20 patient...
September 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28903782/natural-genetic-variation-of-the-cardiac-transcriptome-in-non-diseased-donors-and-patients-with-dilated-cardiomyopathy
#11
Matthias Heinig, Michiel E Adriaens, Sebastian Schafer, Hanneke W M van Deutekom, Elisabeth M Lodder, James S Ware, Valentin Schneider, Leanne E Felkin, Esther E Creemers, Benjamin Meder, Hugo A Katus, Frank Rühle, Monika Stoll, François Cambien, Eric Villard, Philippe Charron, Andras Varro, Nanette H Bishopric, Alfred L George, Cristobal Dos Remedios, Aida Moreno-Moral, Francesco Pesce, Anja Bauerfeind, Franz Rüschendorf, Carola Rintisch, Enrico Petretto, Paul J Barton, Stuart A Cook, Yigal M Pinto, Connie R Bezzina, Norbert Hubner
BACKGROUND: Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. RESULTS: Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 97 patients with dilated cardiomyopathy and 108 non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes...
September 14, 2017: Genome Biology
https://www.readbyqxmd.com/read/28880392/pedal-peptide-orcokinin-type-neuropeptide-signaling-in-a-deuterostome-the-anatomy-and-pharmacology-of-starfish-myorelaxant-peptide-in-asterias-rubens
#12
Ming Lin, Michaela Egertová, Cleidiane G Zampronio, Alexandra M Jones, Maurice R Elphick
Pedal peptide (PP) and orcokinin (OK) are related neuropeptides that were discovered in protostomian invertebrates (mollusks, arthropods). However, analysis of genome/transcriptome sequence data has revealed that PP/OK-type neuropeptides also occur in a deuterostomian phylum-the echinoderms. Furthermore, a PP/OK-type neuropeptide (starfish myorelaxant peptide, SMP) was recently identified as a muscle relaxant in the starfish Patiria pectinifera. Here mass spectrometry was used to identify five neuropeptides (ArPPLN1a-e) derived from the SMP precursor (PP-like neuropeptide precursor 1; ArPPLNP1) in the starfish Asterias rubens...
December 15, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28878122/wnt11-regulates-cardiac-chamber-development-and-disease-during-perinatal-maturation
#13
Marlin Touma, Xuedong Kang, Fuying Gao, Yan Zhao, Ashley A Cass, Reshma Biniwale, Xinshu Xiao, Mansuoreh Eghbali, Giovanni Coppola, Brian Reemtsen, Yibin Wang
Ventricular chamber growth and development during perinatal circulatory transition is critical for functional adaptation of the heart. However, the chamber-specific programs of neonatal heart growth are poorly understood. We used integrated systems genomic and functional biology analyses of the perinatal chamber specific transcriptome and we identified Wnt11 as a prominent regulator of chamber-specific proliferation. Importantly, downregulation of Wnt11 expression was associated with cyanotic congenital heart defect (CHD) phenotypes and correlated with O2 saturation levels in hypoxemic infants with Tetralogy of Fallot (TOF)...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28878117/tead1-is-required-for-maintaining-adult-cardiomyocyte-function-and-its-loss-results-in-lethal-dilated-cardiomyopathy
#14
Ruya Liu, Jeongkyung Lee, Byung S Kim, Qiongling Wang, Samuel K Buxton, Nikhil Balasubramanyam, Jean J Kim, Jianrong Dong, Aijun Zhang, Shumin Li, Anisha A Gupte, Dale J Hamilton, James F Martin, George G Rodney, Cristian Coarfa, Xander Ht Wehrens, Vijay K Yechoor, Mousumi Moulik
Heart disease remains the leading cause of death worldwide, highlighting a pressing need to identify novel regulators of cardiomyocyte (CM) function that could be therapeutically targeted. The mammalian Hippo/Tead pathway is critical in embryonic cardiac development and perinatal CM proliferation. However, the requirement of Tead1, the transcriptional effector of this pathway, in the adult heart is unknown. Here, we show that tamoxifen-inducible adult CM-specific Tead1 ablation led to lethal acute-onset dilated cardiomyopathy, associated with impairment in excitation-contraction coupling...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28861005/murine-myocardial-transcriptome-analysis-reveals-a-critical-role-of-cops8-in-the-gene-expression-of-cullin-ring-ligase-substrate-receptors-and-redox-and-vesicle-trafficking-pathways
#15
Ammara Abdullah, Kathleen M Eyster, Travis Bjordahl, Peng Xiao, Erliang Zeng, Xuejun Wang
Background: The COP9 signalosome (CSN) consisting of 8 unique protein subunits (COPS1 through COPS8) serves as the cullin deneddylase, regulating the catalytic dynamics of cullin RING ligases (CRLs), the largest family of ubiquitin ligases Background: The COP9 signalosome (CSN) consisting of 8 unique protein subunits (COPS1 through COPS8) serves as the cullin deneddylase, regulating the catalytic dynamics of cullin RING ligases (CRLs), the largest family of ubiquitin ligases. Supported primarily by the decrease of substrate receptor (SR) proteins of CRLs in cells deficient of a CSN subunit, CSN-mediated cullin deneddylation is believed to prevent autoubiquitination and self-destruction of the SR in active CRLs...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28860122/exercise-induced-changes-in-glucose-metabolism-promote-physiologic-cardiac-growth
#16
Andrew A Gibb, Paul N Epstein, Shizuka Uchida, Yuting Zheng, Lindsey A McNally, Detlef Obal, Kartik Katragadda, Patrick J Trainor, Daniel J Conklin, Kenneth R Brittian, Michael T Tseng, Jianxun Wang, Steven P Jones, Aruni Bhatnagar, Bradford G Hill
Background -Exercise promotes metabolic remodeling in the heart, which is associated with physiologic cardiac growth; however, it is not known whether or how physical activity-induced changes in cardiac metabolism cause myocardial remodeling. In this study, we tested whether exercise-mediated changes in cardiomyocyte glucose metabolism are important for physiologic cardiac growth. Methods -We used radiometric, immunologic, metabolomic, and biochemical assays to measure changes in myocardial glucose metabolism in mice subjected to acute and chronic treadmill exercise...
August 31, 2017: Circulation
https://www.readbyqxmd.com/read/28859577/single-cell-sequencing-technologies-for-cardiac-stem-cell-studies
#17
Tiantian Liu, Hongjin Wu, Shixiu Wu, Charles Wang
Today with the rapid advancements in stem cell studies and the promising potential of using stem cells in clinical therapy, there is an increasing demand for in-depth comprehensive analysis on individual cell transcriptome and epigenome, as they play critical roles in a number of cell functions such as cell differentiation, growth and reprogramming. The development of single-cell sequencing technologies has helped in revealing some exciting new perspectives in stem cells and regenerative medicine research. Among the various potential applications, single-cell analysis for cardiac stem cells (CSCs) holds tremendous promises in understanding the mechanisms of heart development and regeneration, which might light up the path towards cell therapy for cardiovascular diseases...
August 31, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28854362/loss-of-apela-peptide-in-mice-causes-low-penetrance-embryonic-lethality-and-defects-in-early-mesodermal-derivatives
#18
Laina Freyer, Chih-Wei Hsu, Sonja Nowotschin, Andrea Pauli, Junji Ishida, Keiji Kuba, Akiyoshi Fukamizu, Alexander F Schier, Pamela A Hoodless, Mary E Dickinson, Anna-Katerina Hadjantonakis
Apela (also known as Elabela, Ende, and Toddler) is a small signaling peptide that activates the G-protein-coupled receptor Aplnr to stimulate cell migration during zebrafish gastrulation. Here, using CRISPR/Cas9 to generate a null, reporter-expressing allele, we study the role of Apela in the developing mouse embryo. We found that loss of Apela results in low-penetrance cardiovascular defects that manifest after the onset of circulation. Three-dimensional micro-computed tomography revealed a higher penetrance of vascular remodeling defects, from which some mutants recover, and identified extraembryonic anomalies as the earliest morphological distinction in Apela mutant embryos...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28838933/epigenome-wide-association-study-identifies-cardiac-gene-patterning-and-a-novel-class-of-biomarkers-for-heart-failure
#19
Benjamin Meder, Jan Haas, Farbod Sedaghat-Hamedani, Elham Kayvanpour, Karen Frese, Alan Lai, Rouven Nietsch, Christina Scheiner, Stefan Mester, Diana Martins Bordalo, Ali Amr, Carsten Dietrich, Dietmar Pils, Dominik Siede, Hauke Hund, Andrea Bauer, Daniel Benjamin Holzer, Arjang Ruhparwar, Matthias Mueller-Hennessen, Dieter Weichenhan, Christoph Plass, Tanja Weis, Johannes Backs, Maximilian Wuerstle, Andreas Keller, Hugo A Katus, Andreas E Posch
BACKGROUND: Biochemical DNA modification resembles a crucial regulatory layer among genetic information, environmental factors, and the transcriptome. To identify epigenetic susceptibility regions and novel biomarkers linked to myocardial dysfunction and heart failure, we performed the first multi-omics study in myocardial tissue and blood of patients with dilated cardiomyopathy and controls. METHODS: Infinium human methylation 450 was used for high-density epigenome-wide mapping of DNA methylation in left-ventricular biopsies and whole peripheral blood of living probands...
October 17, 2017: Circulation
https://www.readbyqxmd.com/read/28837672/cardiac-transcriptome-profiling-of-diabetic-akita-mice-using-microarray-and-next-generation-sequencing
#20
Varun Kesherwani, Hamid R Shahshahan, Paras K Mishra
Although diabetes mellitus (DM) causes cardiomyopathy and exacerbates heart failure, the underlying molecular mechanisms for diabetic cardiomyopathy/heart failure are poorly understood. Insulin2 mutant (Ins2+/-) Akita is a mouse model of T1DM, which manifests cardiac dysfunction. However, molecular changes at cardiac transcriptome level that lead to cardiomyopathy remain unclear. To understand the molecular changes in the heart of diabetic Akita mice, we profiled cardiac transcriptome of Ins2+/- Akita and Ins2+/+ control mice using next generation sequencing (NGS) and microarray, and determined the implications of differentially expressed genes on various heart failure signaling pathways using Ingenuity pathway (IPA) analysis...
2017: PloS One
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