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https://www.readbyqxmd.com/read/29681850/-tnfrsf12a-mediated-atherosclerosis-signaling-and-inflammatory-response-as-a-common-protection-mechanism-of-shuxuening-injection-against-both-myocardial-and-cerebral-ischemia-reperfusion-injuries
#1
Ming Lyu, Ying Cui, Tiechan Zhao, Zhaochen Ning, Jie Ren, Xingpiao Jin, Guanwei Fan, Yan Zhu
Shuxuening injection (SXNI) is a widely prescribed herbal medicine of Ginkgo biloba extract (EGB) for cerebral and cardiovascular diseases in China. However, its curative effects on ischemic stroke and heart diseases and the underlying mechanisms remain unknown. Taking an integrated approach of RNA-seq and network pharmacology analysis, we compared transcriptome profiles of brain and heart ischemia reperfusion injury in C57BL/6J mice to identify common and differential target genes by SXNI. Models for myocardial ischemia reperfusion injury (MIRI) by ligating left anterior descending coronary artery (LAD) for 30 min ischemia and 24 h reperfusion and cerebral ischemia reperfusion injury (CIRI) by middle cerebral artery occlusion (MCAO) for 90 min ischemia and 24 h reperfusion were employed to identify the common mechanisms of SXNI on both cerebral and myocardial ischemia reperfusion...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29670885/integrative-bioinformatics-approaches-for-identification-of-drug-targets-in-hypertension
#2
Daiane Hemerich, Jessica van Setten, Vinicius Tragante, Folkert W Asselbergs
High blood pressure or hypertension is an established risk factor for a myriad of cardiovascular diseases. Genome-wide association studies have successfully found over nine hundred loci that contribute to blood pressure. However, the mechanisms through which these loci contribute to disease are still relatively undetermined as less than 10% of hypertension-associated variants are located in coding regions. Phenotypic cell-type specificity analyses and expression quantitative trait loci show predominant vascular and cardiac tissue involvement for blood pressure-associated variants...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29665845/deletion-of-hp1%C3%AE-in-cardiac-myocytes-affects-h4k20me3-levels-but-does-not-impact-cardiac-growth
#3
Kyohei Oyama, Danny El-Nachef, Chen Fang, Hidemi Kajimoto, Jeremy P Brown, Prim B Singh, W Robb MacLellan
BACKGROUND: Heterochromatin, which is formed when tri-methyl lysine 9 of histone H3 (H3K9me3) is bound by heterochromatin 1 proteins (HP1s), plays an important role in differentiation and senescence by silencing cell cycle genes. Cardiac myocytes (CMs) accumulate heterochromatin during differentiation and demethylation of H3K9me3 inhibits cell cycle gene silencing and cell cycle exit in CMs; however, it is unclear if this process is mediated by HP1s. In this study, we created a conditional CM-specific HP1 gamma (HP1γ) knockout (KO) mouse model and tested whether HP1γ is required for cell cycle gene silencing and cardiac growth...
April 17, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29652636/hif1-mediates-a-switch-in-pyruvate-kinase-isoforms-after-myocardial-infarction
#4
Allison Lesher Williams, Vedbar Khadka, Mingxin Tang, Abigail Avelar, Kathryn J Schunke, Mark Menor, Ralph Victor Shohet
Alternative splicing of RNA is an underexplored area of transcriptional response. We expect that early changes in alternatively spliced genes may be important for responses to cardiac injury. Hypoxia inducible factor 1 (HIF1) is a key transcription factor that rapidly responds to loss of oxygen through alteration of metabolism and angiogenesis. The goal of this study was to investigate the transcriptional response after myocardial infarction (MI) and to identify novel, hypoxia-driven changes, including alternative splicing...
April 13, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29610343/transient-fibrosis-resolves-via-fibroblast-inactivation-in-the-regenerating-zebrafish-heart
#5
Héctor Sánchez-Iranzo, María Galardi-Castilla, Andrés Sanz-Morejón, Juan Manuel González-Rosa, Ricardo Costa, Alexander Ernst, Julio Sainz de Aja, Xavier Langa, Nadia Mercader
In the zebrafish ( Danio rerio ), regeneration and fibrosis after cardiac injury are not mutually exclusive responses. Upon cardiac cryoinjury, collagen and other extracellular matrix (ECM) proteins accumulate at the injury site. However, in contrast to the situation in mammals, fibrosis is transient in zebrafish and its regression is concomitant with regrowth of the myocardial wall. Little is known about the cells producing this fibrotic tissue or how it resolves. Using novel genetic tools to mark periostin b - and collagen 1alpha2 ( col1a2 )-expressing cells in combination with transcriptome analysis, we explored the sources of activated fibroblasts and traced their fate...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29596928/cardiac-safety-evaluation-in-zebrafish-and-in-silico-adme-prediction-of-cephalosporins-with-an-aminothiazoyl-ring-at-the-c-7-position
#6
Ying Han, Bo Chen, Jingpu Zhang, Changqin Hu
Systems toxicology approaches have been used as important tools in the drug discovery and medicine quality control processes. The aim of this study was to assess the pharmacokinetic and toxicity properties of cephalosporins with an aminothiazoyl ring at the C-7 position (CATRs). Cardiac toxicity of the compounds was assessed in zebrafish embryos, and it was determined that CATRs disturbed the formation and development of the heart in a dose-dependent manner. Differentially expressed genes (DEGs) related to the heart were also identified by transcriptome analysis, and co-DEGs were obtained in the protein-protein interaction (PPI) network...
March 26, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29588317/spatiotemporal-multi-omics-mapping-generates-a-molecular-atlas-of-the-aortic-valve-and-reveals-networks-driving-disease
#7
Florian Schlotter, Arda Halu, Shinji Goto, Mark C Blaser, Simon C Body, Lang H Lee, Hideyuki Higashi, Daniel M DeLaughter, Joshua D Hutcheson, Payal Vyas, Tan Pham, Maximillian A Rogers, Amitabh Sharma, Christine E Seidman, Joseph Loscalzo, Jonathan G Seidman, Masanori Aikawa, Sasha A Singh, Elena Aikawa
Background -No pharmacological therapy exists for calcific aortic valve disease (CAVD), which confers a dismal prognosis without invasive valve replacement. The search for therapeutics and early diagnostics is challenging since CAVD presents in multiple pathological stages. Moreover, it occurs in the context of a complex, multi-layered tissue architecture, a rich and abundant extracellular matrix phenotype, and a unique, highly plastic and multipotent resident cell population. Methods -A total of 25 human stenotic aortic valves obtained from valve replacement surgeries were analyzed by multiple modalities, including transcriptomics and global unlabeled and label-based tandem-mass-tagged proteomics...
March 27, 2018: Circulation
https://www.readbyqxmd.com/read/29579159/reactivation-of-the-nkx2-5-cardiac-enhancer-after-myocardial-infarction-does-not-presage-myogenesis
#8
Marcus-André Deutsch, Stefanie A Doppler, Xinghai Li, Harald Lahm, Gianluca Santamaria, Giovanni Cuda, Stefan Eichhorn, Thomas Ratschiller, Elda Dzilic, Martina Dreßen, Annekathrin Eckart, Konstantin Stark, Steffen Massberg, Anna Bartels, Christoph Rischpler, Ralf Gilsbach, Lutz Hein, Bernd K Fleischmann, Sean M Wu, Rüdiger Lange, Markus Krane
Aims: The contribution of resident stem or progenitor cells to cardiomyocyte renewal after injury in adult mammalian hearts remains a matter of considerable debate. We evaluated a cell population in the adult mouse heart induced by myocardial infarction (MI) and characterized by an activated Nkx2.5 enhancer element that is specific for multipotent cardiac progenitor cells during embryonic development. We hypothesized that these MI induced cells (MICs) harbor cardiomyogenic properties similar to their embryonic counterparts...
March 20, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29560432/altered-regulation-of-cardiac-ankyrin-repeat-protein-in-heart-failure
#9
Amber Kempton, Matt Cefalu, Cody Justice, Tesla Baich, Mohamed Derbala, Benjamin Canan, Paul M L Janssen, Peter J Mohler, Sakima A Smith
Background: Left ventricular assist devices (LVADs) have revolutionized and improved the care of the sickest heart failure (HF) patients, and it is imperative that they receive appropriate ventricular unloading. Assessing this critical parameter with current methodologies (labs, imaging) is usually suboptimal in this patient population. Hence it is imperative to elucidate the molecular underpinnings involved in ventricular unloading. We have previously identified the cytoskeletal protein βII spectrin as an essential nodal protein involved in post-translational targeting and βII spectrin protein levels are significantly altered in multiple forms of human and animal HF...
January 2018: Heliyon
https://www.readbyqxmd.com/read/29556499/-in-silico-analysis-of-differential-gene-expression-in-three-common-rat-models-of-diastolic-dysfunction
#10
Raffaele Altara, Fouad A Zouein, Rita Dias Brandão, Saeed N Bajestani, Alessandro Cataliotti, George W Booz
Standard therapies for heart failure with preserved ejection fraction (HFpEF) have been unsuccessful, demonstrating that the contribution of the underlying diastolic dysfunction pathophysiology differs from that of systolic dysfunction in heart failure and currently is far from being understood. Complicating the investigation of HFpEF is the contribution of several comorbidities. Here, we selected three established rat models of diastolic dysfunction defined by three major risk factors associated with HFpEF and researched their commonalities and differences...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29550018/a-dimeric-thymosin-beta-4-with-novel-bio-activity-protects-post-ischemic-cardiac-function-by-accelerating-vascular-endothelial-cell-proliferation
#11
Qiang Hao, Lei He, Jiming Zhou, Yuan Yuan, Xiaowen Ma, Zhijun Pang, Weina Li, Yingqi Zhang, Wei Zhang, Cun Zhang, Meng Li
BACKGROUND: Thymosin beta 4 (Tβ4) is a 43-amino-acid peptide with protective properties in myocardium injury. Previously, we produced a recombinant human dimeric Tβ4 (DTβ4). Here, the cardioprotective effects of DTβ4 and the molecular mechanisms underlying its enhanced activity were investigated. METHODS AND RESULTS: Echocardiography measurements showed that the cardioprotective effect of DTβ4 in myocardial infarction mice was significantly higher than that of wild-type Tβ4...
June 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29549296/mechanical-stretch-induced-transcriptomic-profiles-in-cardiac-myocytes
#12
Jaana Rysä, Heikki Tokola, Heikki Ruskoaho
Mechanical forces are able to activate hypertrophic growth of cardiomyocytes in the overloaded myocardium. However, the transcriptional profiles triggered by mechanical stretch in cardiac myocytes are not fully understood. Here, we performed the first genome-wide time series study of gene expression changes in stretched cultured neonatal rat ventricular myocytes (NRVM)s, resulting in 205, 579, 737, 621, and 1542 differentially expressed (>2-fold, P < 0.05) genes in response to 1, 4, 12, 24, and 48 hours of cyclic mechanical stretch...
March 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29531803/glucose-6-phosphate-dehydrogenase-is-critical-for-suppression-of-cardiac-hypertrophy-by-h-2-s
#13
Aastha Chhabra, Shalini Mishra, Gaurav Kumar, Asheesh Gupta, Gaurav Kumar Keshri, Brij Bharti, Ram Niwas Meena, Amit Kumar Prabhakar, Dinesh Kumar Singh, Kalpana Bhargava, Manish Sharma
Hydrogen Sulfide (H2 S), recently identified as the third endogenously produced gaseous messenger, is a promising therapeutic prospect for multiple cardio-pathological states, including myocardial hypertrophy. The molecular niche of H2 S in normal or diseased cardiac cells is, however, sparsely understood. Here, we show that β-adrenergic receptor (β-AR) overstimulation, known to produce hypertrophic effects in cardiomyocytes, rapidly decreased endogenous H2 S levels. The preservation of intracellular H2 S levels under these conditions strongly suppressed hypertrophic responses to adrenergic overstimulation, thus suggesting its intrinsic role in this process...
December 2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29506241/pitx2-deficiency-and-associated-human-disease-insights-from-the-zebrafish-model
#14
Kathryn E Hendee, Elena A Sorokina, Sanaa S Muheisen, Linda M Reis, Rebecca C Tyler, Vujica Markovic, Goran Cuturilo, Brian A Link, Elena V Semina
The PITX2 (paired-like homeodomain 2) gene encodes a bicoid-like homeodomain transcription factor linked with several human disorders. The main associated congenital phenotype is Axenfeld-Rieger syndrome, type 1 (ARS), an autosomal dominant condition characterized by variable defects in the anterior segment of the eye, an increased risk of glaucoma, craniofacial dysmorphism and dental and umbilical anomalies; in addition to this, one report implicated PITX2 in ring dermoid of the cornea and a few others described cardiac phenotypes...
March 1, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29495457/microrna-and-transcriptomic-profiling-showed-mirna-dependent-impairment-of-systemic-regulation-and-synthesis-of-biomolecules-in-rag2-ko-mice
#15
Abu Musa Md Talimur Reza, Yun-Jung Choi, Jin-Hoi Kim
The Rag2 knockout (KO) mouse is a well-established immune-compromised animal model for biomedical research. A comparative study identified the deregulated expression of microRNAs (miRNAs) and messenger RNAs (mRNAs) in Rag2 KO mice. However, the interaction between deregulated genes and miRNAs in the alteration of systemic (cardiac, renal, hepatic, nervous, and hematopoietic) regulations and the synthesis of biomolecules (such as l-tryptophan, serotonin, melatonin, dopamine, alcohol, noradrenaline, putrescine, and acetate) are unclear...
February 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29471264/collective-transcriptomic-deregulation-of-hypertrophic-and-dilated-cardiomyopathy-importance-of-fibrotic-mechanism-in-heart-failure
#16
Beutline Malgija, Nachimuthu Senthil Kumar, Shanmughavel Piramanayagam
Myocardial fibrosis reside a common pathological feature in hypertrophic and dilated cardiomyopathy that results in ventricular dysfunction leading to heart failure. Though several studies reported the role of fibrosis in cardiac diseases, their pathologic mechanisms leading to heart failure remains unclear. A few studies have proposed integrated analysis of microarray information and protein-protein interaction (PPI) systems to discover subnetwork markers related to diagnosis and prognosis of the disease. In addition to PPI networks, we incorporated miRNAs and transcription factors to find the putative miRNAs and transcription factors that might regulate the pathological process and progression of cardiomyopathy and their further progression to heart failure...
February 10, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29457789/a-common-variant-alters-scn5a-mir-24-interaction-and-associates-with-heart-failure-mortality
#17
Xiaoming Zhang, Jin-Young Yoon, Michael Morley, Jared M McLendon, Kranti A Mapuskar, Rebecca Gutmann, Haider Mehdi, Heather L Bloom, Samuel C Dudley, Patrick T Ellinor, Alaa A Shalaby, Raul Weiss, W H Wilson Tang, Christine S Moravec, Madhurmeet Singh, Anne L Taylor, Clyde W Yancy, Arthur M Feldman, Dennis M McNamara, Kaikobad Irani, Douglas R Spitz, Patrick Breheny, Kenneth B Margulies, Barry London, Ryan L Boudreau
SCN5A encodes the voltage-gated Na+ channel NaV1.5 that is responsible for depolarization of the cardiac action potential and rapid intercellular conduction. Mutations disrupting the SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and single-nucleotide polymorphisms (SNPs) linked to SCN5A splicing, localization, and function associate with heart failure-related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. We recently generated a transcriptome-wide map of microRNA (miR) binding sites in human heart, evaluated their overlap with common SNPs, and identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within the SCN5A coding sequence...
March 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29452236/cardiac-and-placental-mitochondrial-characterization-in-a-rabbit-model-of-intrauterine-growth-restriction
#18
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
#19
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
#20
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: Circulation. Genomic and precision medicine
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