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Cardiac mechanics

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https://www.readbyqxmd.com/read/28335032/allele-specific-ablation-rescues-electrophysiological-abnormalities-in-a-human-ips-cell-model-of-long-qt-syndrome-with-a-calm2-mutation
#1
Yuta Yamamoto, Takeru Makiyama, Takeshi Harita, Kenichi Sasaki, Yimin Wuriyanghai, Mamoru Hayano, Suguru Nishiuchi, Hirohiko Kohjitani, Sayako Hirose, Jiarong Chen, Fumika Yokoi, Taisuke Ishikawa, Seiko Ohno, Kazuhisa Chonabayashi, Hideki Motomura, Yoshinori Yoshida, Minoru Horie, Naomasa Makita, Takeshi Kimura
Background: Calmodulin is a ubiquitous Ca 2+ sensor molecule encoded by three distinct calmodulin genes, CALM1-3 . Recently, mutations in CALM1-3 have been reported to be associated with severe early-onset long-QT syndrome (LQTS). However, the underlying mechanism through which heterozygous calmodulin mutations lead to severe LQTS remains unknown, particularly in human cardiomyocytes. Objectives: We aimed to establish an LQTS disease model associated with a CALM2 mutation (LQT15) using human induced pluripotent stem cells (hiPSCs) and to assess mutant allele-specific ablation by genome editing for the treatment of LQT15...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334977/sclip-an-integrated-platform-to-study-rna-protein-interactomes-in-biomedical-research-identification-of-cstf2tau-in-alternative-processing-of-small-nuclear-rnas
#2
Yulia Kargapolova, Michal Levin, Karl Lackner, Sven Danckwardt
RNA-binding proteins (RBPs) are central for gene expression by controlling the RNA fate from birth to decay. Various disorders arising from perturbations of RNA-protein interactions document their critical function. However, deciphering their function is complex, limiting the general functional elucidation of this growing class of proteins and their contribution to (patho)physiology. Here, we present sCLIP, a simplified and robust platform for genome-wide interrogation of RNA-protein interactomes based on crosslinking-immunoprecipitation and high-throughput sequencing...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334560/development-and-preliminary-testing-of-the-coordination-process-error-reporting-tool-cpert-a-prospective-clinical-surveillance-mechanism-for-teamwork-errors-in-the-pediatric-cardiac-icu
#3
Katherine E Bates, Judy A Shea, Geoffrey L Bird, Cynthia Field, Deipanjan Nandi, Robert E Shaddy, Joshua P Metlay
BACKGROUND: Patient safety reporting systems (PSRSs) may not detect teamwork or coordination process errors that affect all dimensions of quality defined by the Institute of Medicine. This study aimed to develop and observe the performance of a novel tool, the Coordination Process Error Reporting Tool (CPERT), as a prospective clinical surveillance mechanism for teamwork errors in the pediatric cardiac ICU. METHODS: Providers and parents used the qualitative nominal group technique to identify coordination process error examples...
December 2016: Joint Commission Journal on Quality and Patient Safety
https://www.readbyqxmd.com/read/28334543/-functional-impact-of-herg-from-physiological-role-to-target-of-anticancer-therapy
#4
Júlia Šatková, Markéta Bébarová
The human ether-à-go-go related gene (hERG; officially designated as KCNH2) encodes the structure of protein forming α-subunit of voltage-gated ion channel which conducts the rapid component of delayed rectifier K+ current (IKr). This current plays an important role namely in the cardiac repolarization. Mutations in hERG result in inherited arrhythmogenic syndromes characterized by a lenghtening or shortening of QT interval on the electrocardiogram and by an increased occurrence of life-threatening arrhythmias...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28334384/the-cancer-paradigms-of-mammalian-regeneration-can-mammals-regenerate-as-amphibians
#5
Rachel Sarig, Eldad Tzahor
Regeneration in mammals is restricted to distinct tissues and occurs mainly by expansion and maturation of resident stem cells. During regeneration, even subtle mutations in the proliferating cells may cause a detrimental effect by eliciting abnormal differentiation or malignant transformation. Indeed, cancer in mammals has been shown to arise through deregulation of stem cells maturation, which often leads to a differentiation block and cell transformation. In contrast, lower organisms such as amphibians retain a remarkable regenerative capacity in various organs, which occurs via de- and re-differentiation of mature cells...
March 15, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28333981/lipopolysaccharide-induced-endotoxemia-in-corn-oil-preloaded-mice-causes-an-extended-course-of-lung-injury-and-repair-and-pulmonary-fibrosis-a-translational-mouse-model-of-acute-respiratory-distress-syndrome
#6
Chaomin Wu, Colin E Evans, Zhiyu Dai, Xiaojia Huang, Xianming Zhang, Hua Jin, Guochang Hu, Yuanlin Song, You-Yang Zhao
Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure, bilateral pulmonary infiltrates, and pulmonary edema of non-cardiac origin. Effective treatments for ARDS patients may arise from experimental studies with translational mouse models of this disease that aim to delineate the mechanisms underlying the disease pathogenesis. Mouse models of ARDS, however, can be limited by their rapid progression from injured to recovery state, which is in contrast to the course of ARDS in humans...
2017: PloS One
https://www.readbyqxmd.com/read/28333941/phenotypically-heterogeneous-podoplanin-expressing-cell-populations-are-associated-with-the-lymphatic-vessel-growth-and-fibrogenic-responses-in-the-acutely-and-chronically-infarcted-myocardium
#7
Maria Cimini, Antonio Cannatá, Gianandrea Pasquinelli, Marcello Rota, Polina Goichberg
Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts...
2017: PloS One
https://www.readbyqxmd.com/read/28333713/micrornas-and-lipid-metabolism
#8
Binod Aryal, Abhishek K Singh, Noemi Rotllan, Nathan Price, Carlos Fernández-Hernando
PURPOSE OF REVIEW: Work over the past decade has identified the important role of microRNAs (miRNAS) in regulating lipoprotein metabolism and associated disorders including metabolic syndrome, obesity, and atherosclerosis. This review summarizes the most recent findings in the field, highlighting the contribution of miRNAs in controlling LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) metabolism. RECENT FINDINGS: A number of miRNAs have emerged as important regulators of lipid metabolism, including miR-122 and miR-33...
March 22, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28333387/pathophysiological-fundamentals-of-diabetic-cardiomyopathy
#9
Xinyue Hu, Tao Bai, Zheng Xu, Qiuju Liu, Yang Zheng, Lu Cai
Diabetic cardiomyopathy (DCM) was first recognized more than four decades ago and occurred independent of cardiovascular diseases or hypertension in both type 1 and type 2 diabetic patients. The exact mechanisms underlying this disease remain incompletely understood. Several pathophysiological bases responsible for DCM have been proposed, including the presence of hyperglycemia, nonenzymatic glycosylation of large molecules (e.g., proteins), energy metabolic disturbance, mitochondrial damage and dysfunction, impaired calcium handling, reactive oxygen species formation, inflammation, cardiac cell death, and cardiac hypertrophy and fibrosis, leading to impairment of cardiac contractile functions...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333383/calcium-transport-and-signaling-in-mitochondria
#10
Roberto Bravo-Sagua, Valentina Parra, Camila López-Crisosto, Paula Díaz, Andrew F G Quest, Sergio Lavandero
Calcium (Ca2+) is a key player in the regulation of many cell functions. Just like Ca2+, mitochondria are ubiquitous, versatile, and dynamic players in determining both cell survival and death decisions. Given their ubiquitous nature, the regulation of both is deeply intertwined, whereby Ca2+ regulates mitochondrial functions, while mitochondria shape Ca2+ dynamics. Deregulation of either Ca2+ or mitochondrial signaling leads to abnormal function, cell damage or even cell death, thereby contributing to muscle dysfunction or cardiac pathologies...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333037/cerebral-hemodynamic-with-intra-aortic-balloon-pump-business-as-usual
#11
Juliana Caldas, Ronney B Panerai, Edson Bor-Seng-Shu, Juliano Almeida, Graziela Ferreira, Ligia Cunha, Ricardo Nogueira, Marcelo Oliveira, Fabio Jatene, Thompson Robinson, Ludhmila Hajjar
Intra-aortic balloon pump (IABP) is commonly used as mechanical support after cardiac surgery or cardiac shock. Although its benefits for cardiac function have been well documented, its effects on cerebral circulation are still controversial. We hypothesized that transfer function analysis (TFA) and continuous estimates of dynamic cerebral autoregulation (CA) provide consistent results in the assessment of cerebral autoregulation in patients with IABP. Continuous recordings of blood pressure (BP, intra-arterial line), end-tidal CO2, heart rate and cerebral blood flow velocity (CBFV, transcranial Doppler) were obtained i) 5 minutes with IABP ratio 1:3, ii) 5 minutes, starting 1 minute with the IABP-ON, and continuing for another 4 minutes without pump assistance (IABP-OFF)...
March 23, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28332558/multiple-h-sensors-mediate-the-extracellular-acidification-induced-ca-2-i-elevation-in-cultured-rat-ventricular-cardiomyocytes
#12
Yuan-Lang Hu, Xue Mi, Chao Huang, Hui-Fang Wang, Jian-Ren Song, Qing Shu, Lan Ni, Jian-Guo Chen, Fang Wang, Zhuang-Li Hu
Acidosis has been known to cause "Ca(2+) transients", however, the mechanism is still uncertain. Here, we demonstrated that multiple H(+) sensors, such as ASICs, TRPV1 and proton-sensing G protein coupled receptors (GPCRs) are involved in extracellular acidification-induced intracellular calcium ([Ca(2+)]i) elevation. By using calcium imaging measures, we observed that both ASIC and TRPV1 channels inhibitors suppressed the [Ca(2+)]i elevation induced by extracellular acidosis in cultured rat cardiac myocytes...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332202/calcium-signalling-silencing-in-atrial-fibrillation
#13
Maura Greiser
Sub-cellular calcium signalling silencing is a novel and distinct cellular and molecular adaptive response to rapid cardiac activation. Calcium signalling silencing develops during short-term sustained rapid atrial activation as seen clinically during paroxysmal atrial fibrillation (AF). It is the first 'anti-arrhythmic' adaptive response in the setting of AF and appears to counteract the maladaptive changes that lead to intracellular Ca(2+) signalling instability and Ca(2+) based arrhythmogenicity. Calcium signalling silencing results in a failed propagation of the [Ca(2+) ]i signal to the myocyte centre in both patients with AF and in a rabbit model...
March 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28331977/role-of-plasma-membrane-associated-akaps-for-the-regulation-of-cardiac-ik1-current-by-protein-kinase-a
#14
Claudia Seyler, Daniel Scherer, Christoph Köpple, Martin Kulzer, Sevil Korkmaz, Panagiotis Xynogalos, Dierk Thomas, Ziya Kaya, Eberhard Scholz, Johannes Backs, Christoph Karle, Hugo A Katus, Edgar Zitron
The cardiac IK1 current stabilizes the resting membrane potential of cardiomyocytes. Protein kinase A (PKA) induces an inhibition of IK1 current which strongly promotes focal arrhythmogenesis. The molecular mechanisms underlying this regulation have only partially been elucidated yet. Furthermore, the role of A-kinase anchoring proteins (AKAPs) in this regulation has not been examined to date. The objective of this project was to elucidate the molecular mechanisms underlying the inhibition of IK1 by PKA and to identify novel molecular targets for antiarrhythmic therapy downstream β-adrenoreceptors...
March 22, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28331934/microarray-analysis-of-differential-gene-expression-profile-between-human-fetal-and-adult-heart
#15
Zhimin Geng, Jue Wang, Lulu Pan, Ming Li, Jitai Zhang, Xueli Cai, Maoping Chu
Although many changes have been discovered during heart maturation, the genetic mechanisms involved in the changes between immature and mature myocardium have only been partially elucidated. Here, gene expression profile changed between the human fetal and adult heart was characterized. A human microarray was applied to define the gene expression signatures of the fetal (13-17 weeks of gestation, n = 4) and adult hearts (30-40 years old, n = 4). Gene ontology analyses, pathway analyses, gene set enrichment analyses, and signal transduction network were performed to predict the function of the differentially expressed genes...
March 22, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28331574/microrna-and-thyroid-hormone-signaling-in-cardiac-and-skeletal-muscle
#16
REVIEW
Duo Zhang, Yan Li, Shengnan Liu, Yu-Cheng Wang, Feifan Guo, Qiwei Zhai, Jingjing Jiang, Hao Ying
Thyroid hormone (TH) signaling plays critical roles in the differentiation, growth, metabolism, and physiological function of all organs or tissues, including heart and skeletal muscle. Due to the significant progress in our understanding of the molecular mechanisms that underlie TH action, it's widely accepted that TH signaling is regulated at multiple levels. A growing number of discoveries suggest that microRNAs (miRNAs) act as fine-tune regulators of gene expression and adds sophisticated regulatory tiers to signaling pathways...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28331525/the-anti-ageing-molecule-sirt1-mediates-beneficial-effects-of-cardiac-rehabilitation
#17
Giusy Russomanno, Graziamaria Corbi, Valentina Manzo, Nicola Ferrara, Giuseppe Rengo, Annibale A Puca, Salvatore Latte, Albino Carrizzo, Maria Consiglia Calabrese, Ramaroson Andriantsitohaina, Walter Filippelli, Carmine Vecchione, Amelia Filippelli, Valeria Conti
BACKGROUND: An exercise-based Cardiac Rehabilitation Programme (CRP) is established as adjuvant therapy in heart failure (HF), nevertheless it is underutilized, especially in the elderly. While the functional and hemodynamic effects of CRP are well known, its underlying molecular mechanisms have not been fully clarified. The present study aims to evaluate the effects of a well-structured 4-week CRP in patients with stable HF from a molecular point of view. RESULTS: A prospective longitudinal observational study was conducted on patients consecutively admitted to cardiac rehabilitation...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28330474/hypercholesterolemia-downregulates-autophagy-in-the-rat-heart
#18
Zoltán Giricz, Gábor Koncsos, Tomáš Rajtík, Zoltán V Varga, Tamás Baranyai, Csaba Csonka, Adrián Szobi, Adriana Adameová, Roberta A Gottlieb, Péter Ferdinandy
BACKGROUND: We have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart...
March 23, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28329269/proteomics-highlights-decrease-of-matricellular-proteins-in-left-ventricular-assist-device-therapy%C3%A2
#19
Jasmin Hasmik Shahinian, Bettina Mayer, Stefan Tholen, Kerstin Brehm, Martin L Biniossek, Hannah Füllgraf, Selina Kiefer, Ulrike Heizmann, Claudia Heilmann, Florian Rüter, Martin Grapow, Oliver Thomas Reuthebuch, Friedrich Eckstein, Friedhelm Beyersdorf, Oliver Schilling, Matthias Siepe
OBJECTIVES: We investigated the impact of mechanical unloading with a left ventricular assist device (LVAD) on the myocardial proteome. METHODS: We collected 11 patient-matched samples of myocardial left ventricular tissue of patients with non-ischaemic dilate cardiomyopathy, harvested at time of LVAD implant ('pre-LVAD') and heart transplant ('post-LVAD'). Samples were studied by quantitative proteomics. Further we performed histological assessment of deposited collagens and immune infiltration in both pre- and post-LVAD samples...
February 20, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28329231/cardiac-protective-effects-of-remote-ischaemic-preconditioning-in-children-undergoing-tetralogy-of-fallot-repair-surgery-a-randomized-controlled-trial
#20
Qingping Wu, Tingting Wang, Shiqiang Chen, Quanjun Zhou, Haobo Li, Na Hu, Yinglu Feng, Nianguo Dong, Shanglong Yao, Zhengyuan Xia
Aims: Remote ischaemic preconditioning (RIPC) by inducing brief ischaemia in distant tissues protects the heart against myocardial ischaemia-reperfusion injury (IRI) in children undergoing open-heart surgery, although its effectiveness in adults with comorbidities is controversial. The effectiveness and mechanism of RIPC with respect to myocardial IRI in children with tetralogy of Fallot (ToF), a severe cyanotic congenital cardiac disease, undergoing open heart surgery are unclear. We hypothesized that RIPC can confer cardioprotection in children undergoing ToF repair surgery...
February 18, 2017: European Heart Journal
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