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https://www.readbyqxmd.com/read/28812984/modelling-the-effects-of-quinidine-disopyramide-and-e-4031-on-short-qt-syndrome-variant-3-in-the-human-ventricles
#1
Cunjin Luo, Kuanquan Wang, Henggui Zhang
Short QT syndrome (SQTS) is an inherited cardiac channelopathy, but at present little information is available on its pharmacological treatment. SQT3 variant (linked to the inward rectifier potassium current IK1) of SQTS, results from a gain-of-function mutation (Kir2.1 D172N) in the KCNJ2-encoded channels, which is associated with ventricular fibrillation (VF). Using biophysically-detailed human ventricular computer models, this study investigated the potential effects of quinidine, disopyramide, and E-4031 on SQT3...
August 16, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28812220/sphingosine-1-phosphate-receptor-modulators-for-the-treatment-of-multiple-sclerosis
#2
REVIEW
Burhan Z Chaudhry, Jeffrey A Cohen, Devon S Conway
Sphingosine 1-phosphate receptor (S1PR) modulators possess a unique mechanism of action in the treatment of multiple sclerosis (MS). Subtype 1 of the S1PR is expressed on the surface of lymphocytes and is important in regulating egression from lymph nodes. The S1PR modulators indirectly antagonize the receptor's function leading to sequestration of lymphocytes in the lymph nodes. Fingolimod was the first S1PR modulator to receive regulatory approval for relapsing-remitting MS after 2 phase III trials demonstrated potent efficacy, safety, and tolerability...
August 15, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28807154/total-internal-reflectance-fluorescence-imaging-of-genetically-engineered-ryanodine-receptor-targeted-ca-2-probes-in-rat-ventricular-myocytes
#3
Sara Pahlavan, Marin Morad
The details of cardiac Ca(2+) signaling within the dyadic junction remain unclear because of limitations in rapid spatial imaging techniques, and availability of Ca(2+) probes localized to dyadic junctions. To critically monitor ryanodine receptors' (RyR2) Ca(2+) nano-domains, we combined the use of genetically engineered RyR2-targeted pericam probes, (FKBP-YCaMP, Kd=150nM, or FKBP-GCaMP6, Kd=240nM) with rapid total internal reflectance fluorescence (TIRF) microscopy (resolution, ∼80nm). The punctate z-line patterns of FKBP,(2)-targeted probes overlapped those of RyR2 antibodies and sharply contrasted to the images of probes targeted to sarcoplasmic reticulum (SERCA2a/PLB), or cytosolic Fluo-4 images...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28806493/olaparib-a-clinically-used-poly-adp-ribose-polymerase-inhibitor-protects-against-oxidant-induced-cardiac-myocyte-death-in-vitro-and-improves-cardiac-contractility-during-early-phase-after-heart-transplantation-in-a-rat-model-in-vivo
#4
Sevil Korkmaz-Icöz, Bartosz Szczesny, Michela Marcatti, Shiliang Li, Mihály Ruppert, Felix Lasitschka, Sivakkanan Loganathan, Csaba Szabo, Gábor Szabó
BACKGROUND AND PURPOSE: Olaparib, rucaparib and niraparib, potent inhibitors of poly(ADP-ribose) polymerase (PARP) have recently been approved for human use for oncological indications. Considering the previously demonstrated role of PARP in various forms of acute and chronic myocardial injury, we tested the effect of olaparib in in-vitro models of oxidative stress in cardiomyocytes, and in an in-vivo model of cardiac transplantation. EXPERIMENTAL APPROACH: H9c2-embryonic rat heart-derived myoblasts pretreated with vehicle or olaparib (10μM) were challenged with either hydrogen-peroxide (H2 O2 ) or with glucose-oxidase (GOx, which generates H2 O2 in the tissue culture medium)...
August 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28803513/mechanisms-of-unexpected-death-and-autopsy-findings-in-friedreich-ataxia
#5
Roger W Byard, John D Gilbert
A 36-year-old woman with a clinical history of Friedreich ataxia and hypertrophic cardiomyopathy was found unexpectedly dead at her home. The heart showed asymmetric left ventricular hypertrophy, with an interventricular septal thickness of 20-25 mm (the remainder of the left ventricular wall measured 15 mm). Histologically, both ventricles had irregular areas of marked myocyte hypertrophy with associated interstitial fibrosis and focal myofibre disarray. There was neuronal loss within the dentate nucleus of the cerebellum, with vacuolation and axonal loss in the dorsal columns and spinocerebellar tracts of the upper cervical spinal cord...
January 1, 2017: Medicine, Science, and the Law
https://www.readbyqxmd.com/read/28802249/high-resolution-mapping-of-chromatin-conformation-in-cardiac-myocytes-reveals-structural-remodeling-of-the-epigenome-in-heart-failure
#6
Manuel Rosa-Garrido, Douglas J Chapski, Anthony D Schmitt, Todd H Kimball, Elaheh Karbassi, Emma Monte, Enrique Balderas, Matteo Pellegrini, Tsai-Ting Shih, Elizabeth Soehalim, David A Liem, Peipei Ping, Niels J Galjart, Shuxun Ren, Yibin Wang, Bing Ren, Thomas M Vondriska
Background -Cardiovascular disease is associated with epigenomic changes in the heart, however the endogenous structure of cardiac myocyte chromatin has never been determined. Methods -To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype...
August 11, 2017: Circulation
https://www.readbyqxmd.com/read/28801517/effect-of-densely-ionizing-radiation-on-cardiomyocyte-differentiation-from-human-induced-pluripotent-stem-cells
#7
Erdene Baljinnyam, Sundararajan Venkatesh, Richard Gordan, Satvik Mareedu, Jianyi Zhang, Lai-Hua Xie, Edouard I Azzam, Carolyn K Suzuki, Diego Fraidenraich
The process of human cardiac development can be faithfully recapitulated in a culture dish with human pluripotent stem cells, where the impact of environmental stressors can be evaluated. The consequences of ionizing radiation exposure on human cardiac differentiation are largely unknown. In this study, human-induced pluripotent stem cell cultures (hiPSCs) were subjected to an external beam of 3.7 MeV α-particles at low mean absorbed doses of 0.5, 3, and 10 cGy. Subsequently, the hiPSCs were differentiated into beating cardiac myocytes (hiPSC-CMs)...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28796841/single-cell-qpcr-reveals-that-additional-hand2-and-microrna-1-facilitate-the-early-reprogramming-progress-of-seven-factor-induced-human-myocytes
#8
Emre Bektik, Adrienne Dennis, Prateek Prasanna, Anant Madabhushi, Ji-Dong Fu
The direct reprogramming of cardiac fibroblasts into induced cardiomyocyte (CM)-like cells (iCMs) holds great promise in restoring heart function. We previously found that human fibroblasts could be reprogrammed toward CM-like cells by 7 reprogramming factors; however, iCM reprogramming in human fibroblasts is both more difficult and more time-intensive than that in mouse cells. In this study, we investigated if additional reprogramming factors could quantitatively and/or qualitatively improve 7-factor-mediated human iCM reprogramming by single-cell quantitative PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28796250/p53-mediated-mir-18-repression-activates-hsf2-for-igf-iir-dependent-myocyte-hypertrophy-in-hypertension-induced-heart-failure
#9
Chih-Yang Huang, Pei-Ying Pai, Chia-Hua Kuo, Tsung-Jung Ho, Jing-Ying Lin, Ding-Yu Lin, Fu-Jen Tsai, V Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang
Hypertension-induced cardiac hypertrophy and attenuated cardiac function are the major characteristics of early stage heart failure. Cardiomyocyte death in pathological cardiac conditions is the primary cause of heart failure and mortality. Our previous studies found that heat shock factor 1 (HSF1) protected cardiomyocytes from death by suppressing the IGF-IIR signaling pathway, which is critical for hypertensive angiotensin II-induced cardiomyocyte apoptosis. However, the role of heat shock factor 2 (HSF2) in hypertension-induced cardiac hypertrophy is unknown...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28796037/functional-prediction-of-mir-3144-5p-in-human-cardiac-myocytes-based-on-transcriptome-sequencing-and-bioinformatics
#10
Lei Ruan, Yi Yang, Yi Huang, Ling Ding, Cuntai Zhang, Xiaofen Wu
BACKGROUND: RAN guanine nucleotide release factor (RANGRF) encoding protein MOG1 plays an important role in cardiac arrhythmia, so we intended to investigate the regulatory miRNA of RANGRF and explore its potential regulatory mechanism in arrhythmogenesis. METHODS: Based on bioinformatic analysis, miR-3144-5p was predicted to be a regulatory miRNA of RANGRF, which were then validated through a dual-luciferase reporter plasmid assay. Subsequently, the expression level of miR-3144-5p in human cardiac myocytes (HCMs) was detected, followed by cell transfection with miR-3144-5p mimics...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28789938/azilsartan-ameliorates-diabetic-cardiomyopathy-in-young-db-db-mice-through-the-modulation-of-ace-2-ang-1-7-mas-receptor-cascade
#11
Vijayakumar Sukumaran, Hirotsugu Tsuchimochi, Eisuke Tatsumi, Mikiyasu Shirai, James T Pearson
Hyperglycemia up-regulates intracellular angiotensin II (ANG-II) production in cardiac myocytes. This study investigated the hemodynamic and metabolic effects of azilsartan (AZL) treatment in a mouse model of diabetic cardiomyopathy and whether the cardioprotective effects of AZL are mediated by the angiotensin converting enzyme (ACE)-2/ANG 1-7/Mas receptor (R) cascade. Control db/+ and db/db mice (n=5 per group) were treated with vehicle or AZL (1 or 3 mg/kg/d oral gavage) from the age of 8 to 16 weeks. Echocardiography was then performed and myocardial protein levels of ACE-2, Mas R, AT1R, AT2R, osteopontin, connective tissue growth factor (CTGF), atrial natriuretic peptide (ANP) and nitrotyrosine were measured by Western blotting...
August 5, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28782583/age-related-remodeling-of-the-jak-stat-socs-signaling-pathway-and-associated-myocardial-changes-from-histological-to-molecular-level
#12
Basma Emad Aboulhoda
BACKGROUND: The cellular and molecular mechanisms implicated in age-associated changes in myocardial structure are of paramount importance since they cause profound alterations in the functional response and represent targets for alleviating age-related pathologies. One of these mechanisms is the JAK/STAT/SOCS signaling pathway. AIM OF THE STUDY: The present study is designed to elucidate age-dependent changes of the myocardium to provide morphological basis displaying the pathogenesis of myocardial hypertrophy, fibrosis and inflammation with aging...
August 4, 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/28782532/ghrelin-protects-the-heart-against-ischemia-reperfusion-injury-via-inhibition-of-tlr4-nlrp3-inflammasome-pathway
#13
Qin Wang, Ping Lin, Peng Li, Li Fen, Qian Ren, Xiaofeng Xie, Jing Xu
AIMS: The aim of this study was to investigate the cardioprotective effects of ghrelin against myocardial ischemia/reperfusion (I/R) injury and the underlying mechanism. MAIN METHODS: Sprague-Dawley rats were randomized into Sham, I/R and I/R+ghrelin groups. After 30 minutes ischemia, ghrelin (8nmol/kg) was injected intraperitoneally at the time of reperfusion in the I/R+ghrelin group. Then hemodynamic parameters were observed at 24h after reperfusion. KEY FINDINGS: Ghrelin exhibited dramatic improvement in cardiac functions, as manifested by increased LVSP and ±dP/dtmax and decreased LVDP...
August 4, 2017: Life Sciences
https://www.readbyqxmd.com/read/28780067/novel-large-particle-facs-purification-of-adult-ventricular-myocytes-reveals-accumulation-of-myosin-and-actin-disproportionate-to-cell-size-and-proteome-in-normal-post-weaning-development
#14
Javier E López, Janhavi Sharma, Jorge Avila, Taylor S Wood, Jonathan Van Dyke, Bridget Mclaughlin, Craig Abbey, Andrew Wong, Bat-Erdene Myagmar, Philip M Swigart, Paul C Simpson, Nipavan Chiamvimonvat
RATIONALE: Quantifying cellular proteins in ventricular myocytes (MCs) is challenging due to tissue heterogeneity and the variety of cell sizes in the heart. In post-weaning cardiac ontogeny, rod-shaped MCs make up the majority of the cardiac mass while remaining a minority of cardiac cells in number. Current biochemical analyses of cardiac proteins do not correlate well the content of MC-specific proteins to cell type or size in normally developing tissue. OBJECTIVE: To develop a new MC-specific large-particle fluorescent-activated cell sorting (LP-FACS) strategy for the purification of adult rod-shaped MCs...
August 2, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28777937/upstairs-downstairs-atrial-and-ventricular-cardiac-myocytes-from-human-pluripotent-stem-cells
#15
Michael D Schneider
Cardiomyocyte creation by human pluripotent stem cells (hPSCs) has generated opportunities for heart repair, disease modeling, and drug development. In this issue of Cell Stem Cell,Lee et al. (2017) report prospective markers of atrial versus ventricular myocyte formation from hPSCs and their use in directed differentiation of cardiac sub-lineages.
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28777255/endogenous-and-agonist-induced-opening-of-mitochondrial-big-vs-small-ca2-sensitive-k-channels-on-cardiac-cell-and-mitochondrial-protection
#16
David F Stowe, Meiying Yang, James S Heisner, Amadou K S Camara
Both big (BKCa) and small (SKCa) conductance Ca-sensitive K channels are present in mammalian cardiac cell mitochondria (m). We used pharmacological agonists and antagonists of BKCa and SKCa channels to examine the importance of endogenous opening of these channels and the relative contribution of either or both of these channels to protect against contractile dysfunction and reduce infarct size after ischemia reperfusion (IR) injury through a mitochondrial protective mechanism. Following global cardiac IR injury of ex vivo perfused guinea pig hearts we found the following: both agonists NS1619 (for BKCa) and DCEB (for SKCa) improved contractility; BKCa antagonist paxilline (PAX) alone or with SKCa antagonist NS8593 worsened contractility and enhanced infarct size; both antagonists PAX and NS8593 obliterated protection by their respective agonists; BKCa and SKCa antagonists did not block protection afforded by SKCa and BKCa agonists, respectively; and all protective effects by the agonists were blocked by scavenging superoxide anions (O2) with TBAP...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28776188/alterations-of-relaxin-and-its-receptor-system-components-in-experimental-diabetic-cardiomyopathy-rats
#17
Xiaohui Zhang, Liya Pan, Kelaier Yang, Yu Fu, Yue Liu, Wenjia Chen, Xiao Ma, Xinhua Yin
High glucose induces apoptosis of cardiomyocytes and fibrosis of cardiac fibroblasts, contributing to diabetic cardiomyopathy. In this work, we explore the production of relaxin alterations and the significance of their receptor system components in the hearts of experimental diabetic cardiomyopathy rats. We measured rat relaxin-1 (equivalent to human relaxin-2), relaxin-3, RXFP1 and RXFP3 mRNA expression in the hearts of experimental diabetic cardiomyopathy rats. Neonatal rat ventricular myocytes (NRVMs) and cardiac fibroblasts were treated with 5...
August 3, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28772272/vascularized-cardiac-spheroids-as-novel-3d-in-vitro-models-to-study-cardiac-fibrosis
#18
Gemma A Figtree, Kristen J Bubb, Owen Tang, Eddy Kizana, Carmine Gentile
Spheroid cultures are among the most explored cellular biomaterials used in cardiovascular research, due to their improved integration of biochemical and physiological features of the heart in a defined architectural three-dimensional microenvironment when compared to monolayer cultures. To further explore the potential use of spheroid cultures for research, we engineered a novel in vitro model of the heart with vascularized cardiac spheroids (VCSs), by coculturing cardiac myocytes, endothelial cells, and fibroblasts isolated from dissociated rat neonatal hearts (aged 1-3 days) in hanging drop cultures...
August 4, 2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28772050/the-neuroprotective-agent-rasagiline-mesylate-attenuates-cardiac-remodeling-after-experimental-myocardial-infarction
#19
Aimilia Varela, Manolis Mavroidis, Michalis Katsimpoulas, Irini Sfiroera, Niki Kappa, Angelica Mesa, Nikolaos G Kostomitsopoulos, Dennis V Cokkinos
AIM: Rasagiline mesylate (N-propargyl-1 (R)-aminoindan) (RG) is a selective, potent irreversible inhibitor of monoamine oxidase-B with cardioprotective and anti-apoptotic properties. We investigated whether it could be cardioprotective in a rat model undergoing experimental myocardial infarction (MI) by permanent ligation of the left anterior descending coronary artery. METHODS AND RESULTS: RG was administered, intraperitoneally, for 28 days (2 mg/kg) starting 24 h after MI induction...
August 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28771943/overexpression-of-integrin-%C3%AE-11-induces-cardiac-fibrosis-in-mice
#20
Andreas Romaine, Ida W Sørensen, Cédric Zeltz, Ning Lu, Pugazendhi Murugan Erusappan, Arne Olav Melleby, Lili Zhang, Bård Bendiksen, Emma Louise Robinson, Jan Magnus Aronsen, Kate M Herum, Håvard Danielsen, Ivar Sjaastad, Geir Christensen, Donald Gullberg
AIM: To understand the role of the collagen-binding integrin α11 in vivo we have used a classical approach of creating a mouse strain overexpressing integrin α11. A transgenic mouse strain overexpressing α11 in muscle tissues was analysed in the current study with special reference to the heart tissue. METHODS: We generated and phenotyped integrin α11 transgenic (TG) mice by echocardiography, magnetic resonance imaging and histology. Wild-type (WT) mice were subjected to aortic banding (AB) and the expression of integrin α11 was measured in flow cytometry sorted cardiomyocytes and non-myocytes...
August 3, 2017: Acta Physiologica
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