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https://www.readbyqxmd.com/read/29227474/a-proteolytic-fragment-of-histone-deacetylase-4-protects-the-heart-from-failure-by-regulating-the-hexosamine-biosynthetic-pathway
#1
Lorenz H Lehmann, Zegeye H Jebessa, Michael M Kreusser, Axel Horsch, Tao He, Mariya Kronlage, Matthias Dewenter, Viviana Sramek, Ulrike Oehl, Jutta Krebs-Haupenthal, Albert H von der Lieth, Andrea Schmidt, Qiang Sun, Julia Ritterhoff, Daniel Finke, Mirko Völkers, Andreas Jungmann, Sven W Sauer, Christian Thiel, Alexander Nickel, Michael Kohlhaas, Michaela Schäfer, Carsten Sticht, Christoph Maack, Norbert Gretz, Michael Wagner, Ali El-Armouche, Lars S Maier, Juan E Camacho Londoño, Benjamin Meder, Marc Freichel, Hermann-Josef Gröne, Patrick Most, Oliver J Müller, Stephan Herzig, Eileen E M Furlong, Hugo A Katus, Johannes Backs
The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP)...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29226818/rate-response-programming-tailored-to%C3%A2-the-force-frequency-relationship-improves-exercise-tolerance-in-chronic-heart-failure
#2
John Gierula, Maria F Paton, Judith E Lowry, Haqeel A Jamil, Rowenna Byrom, Michael Drozd, Jack O Garnham, Richard M Cubbon, David A Cairns, Mark T Kearney, Klaus K Witte
OBJECTIVES: This study sought to examine whether the heart rate (HR) at which the force-frequency relationship (FFR) slope peaks (critical HR) could be used to tailor HR response in chronic heart failure (CHF) patients with cardiac pacemakers and whether this favorably influences exercise capacity. BACKGROUND: CHF secondary to left ventricular (LV) systolic dysfunction is characterized by blunting of the positive relationship between HR and LV contractility known as the FFR...
November 27, 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/29224951/design-and-synthesis-of-sulfonamidophenylethylureas-as-novel-cardiac-myosin-activator
#3
Manoj Manickam, Hitesh B Jalani, Thanigaimalai Pillaiyar, Pulla Reddy Boggu, Niti Sharma, Eeda Venkateswararao, You-Jung Lee, Eun-Seok Jeon, Min-Jeong Son, Sun-Hee Woo, Sang-Hun Jung
To optimize the lead urea scaffold 1 and 2 as selective cardiac myosin ATPase activator, a series of urea derivatives have been synthesized to explore its structure activity relationship. Among them N,N-dimethyl-4-(2-(3-(3-phenylpropyl)ureido)ethyl)benzenesulfonamide (13, CMA = 91.6%, FS = 17.62%; EF = 11.55%), N,N-dimethyl-4-(2-(1-methyl-3-(3-phenylpropyl)ureido)ethyl)benzene sulfonamide (40, CMA = 52.3%, FS = 38.96%; EF = 24.19%) and N,N-dimethyl-4-(2-(3-methyl-3-(3-phenylpropyl)ureido)ethyl)benzenesulfonamide (41, CMA = 47...
October 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29224304/-method-for-recording-tension-changes-of-small-pulmonary-artery-and-vein-using-the-isolated-vessel-tension-measurement-system
#4
X T Wu, M D Kuang, X Ouyang, Y Li, M M Yuan, W J Lu, J Wang, Y Q Chen
Objective: To establish a standardized method for isolated pulmonary artery and vein rings with different diameter, pressure and length, which could provide a more scientific method for in vitro study of pulmonary vessel diseases. Methods: Male SD rats were anesthetized, and the right ventricular systolic pressure were measured. Small pulmonary artery and vein rings with 200-400 μm in diameter and 2 mm in length were prepared by dissecting pulmonary arteries and veins. The pulmonary vessel rings were mounted in the organ bath by 2 stainless steel wires with diameter of 40 μm...
December 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29224235/long-term-cardiovascular-re-programming-by-short-term-perinatal-exposure-to-nicotine-s-main-metabolite-cotinine
#5
Stefano Bastianini, Viviana Lo Martire, Alessandro Silvani, Giovanna Zoccoli, Chiara Berteotti, Hugo Lagercrantz, Anders Arner, Gary Cohen
AIM: Gather "proof-of-concept" evidence of the adverse developmental potential of cotinine (a seemingly benign biomarker of recent nicotine / tobacco smoke exposure). METHODS: Pregnant C57 mice drank nicotine or cotinine-laced water for 6wks from conception (NPRE = 2% saccharin+100μg nicotine/ml; CPRE = 2% saccharin + 10μg cotinine/ml) or 3wks after birth (CPOST = 2% saccharin + 30μg cotinine/ml). Controls drank 2% saccharin (CTRL). At 17±1weeks (male pups; CTRL n=6; CPOST n=6; CPRE n=8; NPRE n=9) we assessed (i) cardiovascular control during sleep; (ii) arterial reactivity ex vivo; (iii) expression of genes involved in arterial constriction / dilation...
December 9, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/29223729/structure-function-analysis-of-the-c-terminal-domain-of-the-type-vi-secretion-tssb-tail-sheath-subunit
#6
Badreddine Douzi, Laureen Logger, Silvia Spinelli, Stéphanie Blangy, Christian Cambillau, Eric Cascales
The Type VI secretion system (T6SS) is a specialized macromolecular complex dedicated to the delivery of protein effectors into both eukaryotic and bacterial cells. The general mechanism of action of the T6SS is similar to the injection of DNA by contractile bacteriophages. The cytoplasmic portion of the T6SS is evolutionarily, structurally and functionally related to the phage tail complex. It is composed of an inner tube made of stacked Hcp hexameric rings, engulfed within a sheath and built on a baseplate...
December 6, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29222822/coronary-microvascular-dysfunction-and-myocardial-contractile-reserve-in-women-with-angina-and-no-obstructive-coronary-artery-disease
#7
Marie M Michelsen, Adam Pena, Naja D Mygind, Jan Bech, Ida Gustafsson, Jens Kastrup, Henrik S Hansen, Nis Høst, Peter R Hansen, Eva Prescott
BACKGROUND: Coronary microvascular dysfunction (CMD) is a potential cause of myocardial ischemia and may affect myocardial function at rest and during stress. We investigated whether CMD was associated with left ventricular diastolic and systolic function at rest and during pharmacologically induced hyperemic stress. METHODS: In a prospective cohort study, we included 963 women with angina, left ventricular ejection fraction (LVEF) >45%, and an invasive coronary angiogram without significant stenosis (<50%)...
December 8, 2017: Echocardiography
https://www.readbyqxmd.com/read/29222766/electrical-velocimetry-for-non-invasive-monitoring-of-the-closure-of-the-ductus-arteriosus-in-preterm-infants
#8
Ana Rodríguez Sánchez de la Blanca, M Sánchez Luna, N González Pacheco, M Arriaga Redondo, N Navarro Patiño
Closure of a patent ductus arteriosus (PDA) in preterm infants modifies cardiac output and induces adaptive changes in the hemodynamic situation. The present study aims to analyze those changes, through a non-invasive cardiac output monitor based on blood electrical velocimetry, in preterm babies. A prospective observational study of preterm infants with a gestational age of less than 28 weeks, and a hemodynamic significant PDA, requires intravenous ibuprofen or surgical closure. All patients were monitored with electrical velocimetry before treatment and through the following 72 h...
December 8, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/29222605/the-endocannabinoid-system-in-cardiovascular-function-novel-insights-and-clinical-implications
#9
REVIEW
Salvador Sierra, Natasha Luquin, Judith Navarro-Otano
RATIONALE: Cardiovascular disease is now recognized as the number one cause of death in the world, and the size of the population at risk continues to increase rapidly. The dysregulation of the endocannabinoid (eCB) system plays a central role in a wide variety of conditions including cardiovascular disorders. Cannabinoid receptors, their endogenous ligands, as well as enzymes conferring their synthesis and degradation, exhibit overlapping distributions in the cardiovascular system. Furthermore, the pharmacological manipulation of the eCB system has effects on blood pressure, cardiac contractility, and endothelial vasomotor control...
December 8, 2017: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
https://www.readbyqxmd.com/read/29222596/the-effects-of-local-forearm-muscle-cooling-on-motor-unit-properties
#10
Matthew M Mallette, Lara A Green, David A Gabriel, Stephen S Cheung
PURPOSE: Muscle cooling impairs maximal force. Using needle electromyography (EMG) to assess motor unit properties during muscle cooling, is limited and equivocal. Therefore, we aimed to determine the impact of local muscle cooling on motor unit firing properties using surface EMG decomposition. METHODS: Twenty participants (12 M, 8 F) completed maximal, evoked, and trapezoidal contractions during thermoneutral and cold muscle conditions. Forearm muscle temperature was manipulated using 10-min neutral (~ 32 °C) or 20-min cold (~ 3 °C) water baths...
December 8, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/29222345/type-vi-secretion-system-sheath-inter-subunit-interactions-modulate-its-contraction
#11
Maximilian Brackmann, Jing Wang, Marek Basler
Secretion systems are essential for bacteria to survive and manipulate their environment. The bacterial type VI secretion system (T6SS) generates the force needed for protein translocation by the contraction of a long polymer called sheath. The sheath is a six-start helical assembly of interconnected VipA/VipB subunits. The mechanism of T6SS sheath contraction is unknown. Here, we show that elongating the N-terminal VipA linker or eliminating charge of a specific VipB residue abolishes sheath contraction and delivery of effectors into target cells...
December 8, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29222115/the-methyltransferase-set9-regulates-tgf-b-1-activation-of-renal-fibroblasts-via-interaction-with-smad3
#12
Victoria G Shuttleworth, Luke Gaughan, Lotfia Nawafa, Caitlin A Mooney, Steven L Cobb, Neil S Sheerin, Ian R Logan
Chronic kidney disease (CKD) is a global socioeconomic problem. It is characterised by the presence of differentiated myofibroblasts that, in response to TGF B-1, produce tissue fibrosis, leading to renal failure. Here we define a novel interaction between the SET9 lysine methyltransferase and SMAD3, the principle mediator of TGF B-1 signalling in myofibroblasts. We show that SET9 deficient fibroblasts exhibit globally altered gene expression profiles in response to TGF B-1, whilst overexpression of SET9 enhances SMAD3 transcriptional activity...
December 8, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29221219/the-paradox-of-the-first-cycle-of-chemotherapy-transient-improvement-of-contractility-and-diastolic-function-after-the-first-cycle-of-anthracycline-based-chemotherapy-a-prospective-clinical-trial
#13
Paweł Stachowiak, Andrzej Wojtarowicz, Marta Milchert-Leszczyńska, Krzysztof Safranow, Michał Falco, Robert Kaliszczak, Zdzisława Kornacewicz-Jach
Aims: Breast cancer is the most common cancer among women, and anthracyclines are the most commonly administered drugs for these patients. Cardiotoxicity is one of the complications, which limits the success of this therapy. Very few studies have evaluated anthracycline toxicities within the first few hours after the first infusion, and the majority of published studies were performed in animal models. The present study aimed to evaluate changes in echocardiographic parameters in women with breast cancer 24 hours after receiving the first dose of an anthracycline...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221195/quantification-of-contractile-mechanics-in-the-rat-heart-from-ventricular-pressure-alone
#14
Chih-Hsien Wang, Ru-Wen Chang, Chun-Yi Chang, Ming-Shiou Wu, Hsien-Li Kao, Liang-Chuan Lai, Tai-Horng Young, Hsi-Yu Yu, Yih-Sharng Chen, Kuo-Chu Chang
To quantitate the contractile mechanics of the heart, the ventricle is considered an elastic chamber with known end-systolic elastance (Ees ). Ees can be calculated from a single pressure-ejected volume curve, which requires simultaneous records of left ventricular (LV) pressure and the aortic flow (Qm). In clinical settings, it is helpful to evaluate patients' cardiac contractile status by using a minimally invasive approach to physiological signal monitoring, wherever possible, such as by using LV pressure alone...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221121/tropomyosin-isoform-tpm2-1-regulates-collective-and-amoeboid-cell-migration-and-cell-aggregation-in-breast-epithelial-cells
#15
HyeRim Shin, Dayoung Kim, David M Helfman
Metastasis dissemination is the result of various processes including cell migration and cell aggregation. These processes involve alterations in the expression and organization of cytoskeletal and adhesion proteins in tumor cells. Alterations in actin filaments and their binding partners are known to be key players in metastasis. Downregulation of specific tropomyosin (Tpm) isoforms is a common characteristic of transformed cells. In this study, we examined the role of Tpm2.1 in non-transformed MCF10A breast epithelial cells in cell migration and cell aggregation, because this isoform is downregulated in primary and metastatic breast cancer as well as various breast cancer cell lines...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220595/dose-dependent-effects-of-tadalafil-and-roflumilast-on-ovalbumin-induced-airway-hyperresponsiveness-in-guinea-pigs
#16
Anna Urbanova, Ivana Medvedova, Martin Kertys, Pavol Mikolka, Petra Kosutova, Daniela Mokra, Juraj Mokrý
INTRODUCTION: Chronic obstructive diseases of airways associated with cough and/or airway smooth muscle hyperresponsiveness are usually treated with bronchodilating and anti-inflammatory drugs. Recently, selective phosphodiesterase (PDE) 4 inhibitors have been introduced into the therapy of chronic obstructive pulmonary disease. Several studies have demonstrated their ability to influence the airway reactivity and eosinophilic inflammation by increasing the intracellular cAMP concentrations also in bronchial asthma...
December 8, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/29219187/integrated-molecular-biochemical-and-physiological-assessment-unravels-key-extraction-method-mediated-influences-on-rat-neonatal-cardiomyocytes
#17
Leonardo Jensen, Elida Neri, Vinicius Bassaneze, Nathalia Corrêa De Almeida Oliveira, Rafael Dariolli, Thiago Lauro Turaça, Débora Levy, Douglas Veronez, Mariana Sacrini Ayres Ferraz, Adriano Mesquita Alencar, Sérgio Paulo Bydlowski, Idágene Aparecida Cestari, José Eduardo Krieger
Neonatal cardiomyocytes are instrumental for disease modeling, but the effects of different cell extraction methods on basic cell biological processes remain poorly understood. We assessed the influence of two popular methods to extract rat neonatal cardiomyocytes, Pre-plating (PP) and Percoll (PC) on cell structure, metabolism, and function. Cardiomyocytes obtained from PP showed higher gene expression for troponins, titin, and potassium and sodium channels compared to PC. Also, PP cells displayed higher levels of troponin I protein...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29218721/functional-characterization-of-a-second-pedal-peptide-orcokinin-type-neuropeptide-signaling-system-in-the-starfish-asterias-rubens
#18
Ming Lin, Michaela Egertová, Cleidiane G Zampronio, Alexandra M Jones, Maurice R Elphick
Molluscan pedal peptides (PP) and arthropod orcokinins (OK) are prototypes of a family of neuropeptides that have been identified in several phyla. Recently, starfish myorelaxant peptide (SMP) was identified as a PP/OK-type neuropeptide in the starfish Patiria pectinifera (phylum Echinodermata). Furthermore, analysis of transcriptome sequence data from the starfish Asterias rubens revealed two PP/OK-type precursors: an SMP-type precursor (A. rubens pedal peptide-like neuropeptide precursor 1; ArPPLNP1) and a second precursor (ArPPLNP2)...
December 8, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29218407/short-vs-long-pulses-for-testing-knee-extensor-neuromuscular-properties-does-it-matter
#19
Caroline Giroux, Boris Roduit, Javier Rodriguez-Falces, Jacques Duchateau, Nicola A Maffiuletti, Nicolas Place
PURPOSE: The present study aimed at comparing knee extensor neuromuscular properties determined with transcutaneous electrical stimulation using two pulse durations before and after a standardized fatigue protocol. METHODS: In the first sub-study, 19 healthy participants (ten women and nine men; 28 ± 5 years) took part to two separate testing sessions involving the characterization of voluntary activation (twitch interpolation technique), muscle contractility (evoked forces by single and paired stimuli), and neuromuscular propagation (M-wave amplitude from vastus lateralis and vastus medialis muscles) obtained at supramaximal intensity with a pulse duration of either 0...
December 7, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/29218065/acute-myocardial-injury-in-a-child-with-duchenne-muscular-dystrophy-pulse-steroid-therapy
#20
Eliza Cinteza, Claudiu Stoicescu, Niculina Butoianu, Mihaela Balgradean, Alin Nicolescu, Matthias Angrés
Heart implication in Duchenne muscular dystrophy usually is present in the form of dilated cardiomyopathy, manifested as heart failure and arrhythmias. To delay progression, including heart deterioration, prednisone is recommended as preventive treatment. We report the case of an 11-year-old boy diagnosed with Duchenne muscular dystrophy at the age of seven, who was on preventive treatment with oral prednisone (0.75 mg/kg/day) and beta blocker (metoprolol, 1 mg/kg/day). Suddenly, the patient presented acute chest pain, vomiting and sweating...
September 2017: Mædica
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