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https://www.readbyqxmd.com/read/28090760/expression-patterns-of-cardiac-aging-in-drosophila
#1
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
#2
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
#3
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
#4
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...
December 27, 2016: Biochimie
https://www.readbyqxmd.com/read/28007739/ischemic-preconditioning-confers-epigenetic-repression-of-mtor-and-induction-of-autophagy-through-g9a-dependent-h3k9-dimethylation
#5
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
#6
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
#7
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
#8
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...
November 16, 2016: Cell Systems
https://www.readbyqxmd.com/read/27834691/zebrafish-model-for-functional-screening-of-flow-responsive-genes
#9
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
#10
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
https://www.readbyqxmd.com/read/27818233/systems-biology-dissection-of-mechanisms-and-chemical-basis-of-herbal-formula-in-treating-chronic-myocardial-ischemia
#11
Shuzhen Guo, Peng Li, Bangze Fu, Wenjing Chuo, Kuo Gao, Wuxia Zhang, Junyao Wang, Jianxin Chen, Wei Wang
Herbal medicine is a mixture of multiple compounds, and is intended to exhibit therapeutic effects by attacking multiple disease-causing modules simultaneously. However, it is still a challenge for scientists to untangle the complex biological mechanisms and underlying material basis of herbal medicine. Here, this study was designed to build a systems-biology platform for exploring the molecular mechanisms and corresponding active compounds, with a typical example applied to an herbal formula Qishenkel (QSKL) in the treatment of chronic myocardial ischemia...
December 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27812527/a-novel-murine-model-of-parvovirus-associated-dilated-cardiomyopathy-induced-by-immunization-with-vp1-unique-region-of-parvovirus-b19
#12
Julijus Bogomolovas, Egidijus Šimoliūnas, Ieva Rinkūnaitė, Luka Smalinskaitė, Andrej Podkopajev, Daiva Bironaitė, Cleo-Aron Weis, Alexander Marx, Virginija Bukelskienė, Norbert Gretz, Virginija Grabauskienė, Dittmar Labeit, Siegfried Labeit
Background. Parvovirus B19 (B19V) is a common finding in endomyocardial biopsy specimens from myocarditis and dilated cardiomyopathy patients. However, current understanding of how B19V is contributing to cardiac damage is rather limited due to the lack of appropriate mice models. In this work we demonstrate that immunization of BALB/c mice with the major immunogenic determinant of B19V located in the unique sequence of capsid protein VP1 (VP1u) is an adequate model to study B19V associated heart damage. Methods and Results...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27807997/adenosine-receptors-expression-in-cardiac-fibroblasts-of-patients-with-left-ventricular-dysfunction-due-to-valvular-disease
#13
Silvia Del Ry, Manuela Cabiati, Veronica Della Latta, Stefania Zimbone, Mariarita Natale, Pietro Enea Lazzerini, Francesco Diciolla, Pier Leopoldo Capecchi, Franco Laghi-Pasini, Maria Aurora Morales
CONTEXT: Adenosine restores tissue homeostasis through the interaction with its membrane receptors (AR) expressed on fibroblasts, endothelial cells, smooth muscle cells and leukocytes, but their modulation is still not fully understood. OBJECTIVE: To evaluate whether changes in the transcriptomic profiling of adenosine receptors (AR) occur in cardiac fibroblasts (CF) of patients (pts) with LV dysfunction due to valvular disease (V). The secondary aim was to compare in the same pts the results obtained at cardiac level with those found in circulating leukocytes...
November 3, 2016: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/27805817/the-role-of-tgf-beta-and-ppar-alpha-signalling-pathways-in-radiation-response-of-locally-exposed-heart-integrated-global-transcriptomics-and-proteomics-analysis
#14
Vikram Subramanian, Ingar Seemann, Juliane Merl-Pham, Stefanie M Hauck, Fiona Anne Stewart, Michael J Atkinson, Soile Tapio, Omid Azimzadeh
Epidemiological data from patients undergoing radiotherapy for thoracic tumours clearly show the damaging effect of ionising radiation on cardiovascular system. The long-term impairment of heart function and structure after local high-dose irradiation is associated with systemic inflammatory response, contraction impairment, microvascular damage and cardiac fibrosis. The goal of the present study was to investigate molecular mechanisms involved in this process. C57BL/6J mice received a single X-ray dose of 16 Gy given locally to the heart at the age of 8 weeks...
November 2, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27789736/impact-of-myh6-variants-in-hypoplastic-left-heart-syndrome
#15
Aoy Tomita-Mitchell, Karl D Stamm, Donna K Mahnke, Min-Su Kim, Pip M Hidestrand, Huan Ling Liang, Mary A Goetsch, Mats Hidestrand, Pippa Simpson, Andrew N Pelech, James S Tweddell, D Woodrow Benson, John W Lough, Michael E Mitchell
Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene...
December 1, 2016: Physiological Genomics
https://www.readbyqxmd.com/read/27759042/neonatal-cardiac-dysfunction-and-transcriptome-changes-caused-by-the-absence-of-celf1
#16
Jimena Giudice, Zheng Xia, Wei Li, Thomas A Cooper
The RNA binding protein Celf1 regulates alternative splicing in the nucleus and mRNA stability and translation in the cytoplasm. Celf1 is strongly down-regulated during mouse postnatal heart development. Its re-induction in adults induced severe heart failure and reversion to fetal splicing and gene expression patterns. However, the impact of Celf1 depletion on cardiac transcriptional and posttranscriptional dynamics in neonates has not been addressed. We found that homozygous Celf1 knock-out neonates exhibited cardiac dysfunction not observed in older homozygous animals, although homozygous mice are smaller than wild type littermates throughout development...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27748060/developmental-regulation-of-rna-processing-by-rbfox-proteins
#17
REVIEW
John G Conboy
The Rbfox genes encode an ancient family of sequence-specific RNA binding proteins (RBPs) that are critical developmental regulators in multiple tissues including skeletal muscle, cardiac muscle, and brain. The hallmark of Rbfox proteins is a single high-affinity RRM domain, highly conserved from insects to humans, that binds preferentially to UGCAUG motifs at diverse regulatory sites in pre-mRNA introns, mRNA 3'UTRs, and pre-miRNAs hairpin structures. Versatile regulatory circuits operate on Rbfox pre-mRNA and mRNA to ensure proper expression of Rbfox1 protein isoforms, which then act on the broader transcriptome to regulate alternative splicing networks, mRNA stability and translation, and microRNA processing...
October 17, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27747100/altered-left-ventricular-ion-channel-transcriptome-in-a-high-fat-fed-rat-model-of-obesity-insight-into-obesity-induced-arrhythmogenesis
#18
Reza Ashrafi, Marianne Yon, Lucy Pickavance, Joseph Yanni Gerges, Gershan Davis, John Wilding, Kun Jian, Henggui Zhang, George Hart, Mark Boyett
Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR...
2016: Journal of Obesity
https://www.readbyqxmd.com/read/27742689/role-of-microrna-in-metabolic-shift-during-heart-failure
#19
REVIEW
Mark V Pinti, Quincy A Hathaway, John M Hollander
Heart failure (HF) is an end point resulting from a number of disease states. The prognosis for HF patients is poor with survival rates precipitously low. Energy metabolism is centrally linked to the development of HF, and it involves the proteomic remodeling of numerous pathways, many of which are targeted to the mitochondrion. microRNAs (miRNA) are noncoding RNAs that influence posttranscriptional gene regulation. miRNA have garnered considerable attention for their ability to orchestrate changes to the transcriptome, and ultimately the proteome, during HF...
January 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27717505/emerging-field-of-cardiomics-high-throughput-investigations-into-transcriptional-regulation-of-cardiovascular-development-and-disease
#20
Christopher E Slagle, Frank L Conlon
Congenital heart defects remain a leading cause of infant mortality in the western world, despite decades of research focusing on cardiovascular development and disease. With the recent emergence of several high-throughput technologies including RNA sequencing, chromatin-immunoprecipitation-coupled sequencing, mass-spectrometry-based proteomics analyses, and the numerous variations of these strategies, investigations into cardiac development have been transformed from candidate-based studies into whole-genome, -transcriptome, and -proteome undertakings...
November 2016: Trends in Genetics: TIG
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