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Journal of Molecular and Cellular Cardiology

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https://www.readbyqxmd.com/read/30529267/inhibition-of-brd4-attenuates-transverse-aortic-constriction-and-tgf-%C3%AE-induced-endothelial-mesenchymal-transition-and-cardiac-fibrosis
#1
Shuai Song, Liang Liu, Yi Yu, Rui Zhang, Yigang Li, Wei Cao, Ying Xiao, Guojian Fang, Zhen Li, Xuelian Wang, Qi Wang, Xin Zhao, Long Chen, Yuepeng Wang, Qunshan Wang
Cardiac fibrosis (CF), a process characterized by potentiated proliferation of cardiac fibroblasts and excessive secretion and deposition of extracellular matrix (ECM) from the cells, contributes strongly to the pathogenesis of a series of cardiovascular (CV) diseases, including AMI, heart failure and atrial fibrillation. Endothelial-mesenchymal transition (EndMT), one of the sources of transformed cardiac fibroblasts, has been reported as a key factor involved in CF. However, the molecular basis of EndMT has not been thoroughly elucidated to date...
December 6, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30528909/real-time-local-oxygen-measurements-for-high-resolution-cellular-imaging
#2
Liron Boyman, George S B Williams, Andrew P Wescott, Jennie B Leach, Joseph P Y Kao, W Jonathan Lederer
Single-cell metabolic investigations are hampered by the absence of flexible tools to measure local partial pressure of O2 (pO2 ) at high spatial-temporal resolution. To this end, we developed an optical sensor capable of measuring local pericellular pO2 for subcellular resolution measurements with confocal imaging while simultaneously carrying out electrophysiological and/or chemo-mechanical single cell experiments. Here we present the OxySplot optrode, a ratiometric fluorescent O2 -micro-sensor created by adsorbing O2 -sensitive and O2 -insensitive fluorophores onto micro-particles of silica...
December 5, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30528765/erk-mediated-survival-signaling-is-dependent-on-the-gq-g-protein-coupled-receptor-type-and-subcellular-localization-in-adult-cardiac-myocytes
#3
Erika F Dahl, Steven C Wu, Chastity L Healy, Jocelyn Perry, Timothy D O'Connell
G protein-coupled receptors that signal through Gαq (GqPCRs), like α1-adrenergic and angiotensin receptors (α1-AR, AT-R), are traditionally thought to mediate pathologic remodeling in heart failure, including cardiac myocyte death. However, we previously demonstrated that α1- ARs are cardioprotective and identified an α1A-subtype-ERK survival-signaling pathway in adult cardiac myocytes. Recently, we demonstrated that α1-ARs localize to and signal from the nucleus, whereas AT-R localize to and signal from the sarcolemma in adult cardiac myocytes...
December 4, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30521840/mechanistic-role-of-the-creb-regulated-transcription-coactivator-1-in-cardiac-hypertrophy
#4
Karoline Morhenn, Thomas Quentin, Helen Wichmann, Michael Steinmetz, Maksymilian Prondzynski, Klaus-Dieter Söhren, Torsten Christ, Birgit Geertz, Sabine Schröder, Friedrich A Schöndube, Gerd Hasenfuss, Saskia Schlossarek, Wolfram H Zimmermann, Lucie Carrier, Thomas Eschenhagen, Jean-René Cardinaux, Susanne Lutz, Elke Oetjen
The sympathetic nervous system is the main stimulator of cardiac function. While acute activation of the β-adrenoceptors exerts positive inotropic and lusitropic effects by increasing cAMP and Ca2+ , chronically enhanced sympathetic tone with changed β-adrenergic signaling leads to alterations of gene expression and remodeling. The CREB-regulated transcription coactivator 1 (CRTC1) is activated by cAMP and Ca2+ . In the present study, the regulation of CRTC1 in cardiomyocytes and its effect on cardiac function and growth was investigated...
December 4, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30503754/a-short-history-of-the-development-of-mathematical-models-of-cardiac-mechanics
#5
REVIEW
Steven A Niederer, Kenneth S Campbell, Stuart G Campbell
Cardiac mechanics plays a crucial role in atrial and ventricular function, in the regulation of growth and remodelling, in the progression of disease, and the response to treatment. The spatial scale of the critical mechanisms ranges from nm (molecules) to cm (hearts) with the fastest events occurring in milliseconds (molecular events) and the slowest requiring months (growth and remodelling). Due to its complexity and importance, cardiac mechanics has been studied extensively both experimentally and through mathematical models and simulation...
November 29, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30502350/intra-tracheal-gene-delivery-of-aerosolized-serca2a-to-the-lung-suppresses-ventricular-arrhythmias-in-a-model-of-pulmonary-arterial-hypertension
#6
Benjamin Strauss, Yassine Sassi, Carlos Bueno-Beti, Zeki Ilkan, Nour Raad, Marine Cacheux, Malik Bisserier, Irene C Turnbull, Erik Kohlbrenner, Roger J Hajjar, Lahouaria Hadri, Fadi G Akar
BACKGROUND: Pulmonary arterial hypertension (PAH) results in right ventricular (RV) failure, electro-mechanical dysfunction and heightened risk of sudden cardiac death (SCD), although exact mechanisms and predisposing factors remain unclear. Because impaired chronotropic response to exercise is a strong predictor of early mortality in patients with PAH, we hypothesized that progressive elevation in heart rate can unmask ventricular tachyarrhythmias (VT) in a rodent model of monocrotaline (MCT)-induced PAH...
November 28, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30502349/do-different-nuclei-in-a-binucleated-cardiomyocyte-have-different-rates-of-nuclear-protein-import
#7
Marketa Hlavackova, Elissavet Kardami, Robert Fandrich, Grant N Pierce
The functional significance of having two nuclei in a cell is unknown. Having two stores of genetic material may be advantageous for cell growth. Nuclear protein import is at a critical juncture in the cell to modify cell growth. This study addressed the potential for differential nuclear protein import in two nuclei of the same cell. Isolated adult rat cardiomyocytes were microinjected with an exogenous fluorescent protein conjugated with nuclear localization amino acid sequences to facilitate nuclear import and its detection...
November 28, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30502348/induced-trf2-deletion-leads-to-aging-vascular-phenotype-in-mice-associated-with-arterial-telomere-uncapping-senescence-signaling-and-oxidative-stress
#8
R Garrett Morgan, Ashley E Walker, Daniel W Trott, Daniel R Machin, Grant D Henson, Kelly D Reihl, Richard M Cawthon, Eros L Denchi, Yu Liu, Samuel I Bloom, Tam T Phuong, Russell S Richardson, Lisa A Lesniewski, Anthony J Donato
Age-related vascular dysfunction in large elastic and resistance arteries is associated with reductions in microvascular perfusion and elevations in blood pressure. Recent evidence indicates that telomere uncapping-induced senescence in vascular cells may be an important source of oxidative stress and vascular dysfunction in aging, but the causal relationship between these processes has yet to be elucidated. To test this important unexplored hypothesis, we measured arterial senescence signaling and oxidative stress, carotid and mesenteric artery endothelium-dependent vasodilatory capacity, markers of mesenteric microvascular perfusion and endothelial glycocalyx deterioration, and blood pressure in a novel mouse model of Cre-inducible whole body Trf2 deletion and telomere uncapping...
November 28, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30500377/progression-of-excitation-contraction-coupling-defects-in-doxorubicin-cardiotoxicity
#9
Anna Llach, Marianne Mazevet, Philippe Mateo, Olivier Villejouvert, Audrey Ridoux, C Rucker-Martin, Maxance Ribeiro, Rodolphe Fischmeister, Bertrand Crozatier, Jean-Pierre Benitah, Eric Morel, Ana M Gómez
Cardiac failure is a common complication in cancer survivors treated with anthracyclines. Here we followed up cardiac function and excitation-contraction (EC) coupling in an in vivo doxorubicin (Dox) treated mice model (iv, total dose of 10 mg/Kg divided once every three days). Cardiac function was evaluated by echocardiography at 2, 6 and 15 weeks after the last injection. While normal at 2 and 6 weeks, ejection fraction was significantly reduced at 15 weeks. In order to evaluate the underlying mechanisms, we measured [Ca2+ ]i transients by confocal microscopy and action potentials (AP) by patch-clamp technique in cardiomyocytes isolated at these times...
November 27, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30500376/overexpression-of-tissue-factor-induced-atherothrombosis-in-apolipoprotein-e-mice-via-both-enhanced-plaque-thrombogenicity-and-plaque-instability
#10
Xiaoling Liu, Jing Ma, Lianyue Ma, Fangfang Liu, Cheng Zhang, Yun Zhang, Mei Ni
The mechanisms leading to atherothrombosis from "vulnerable plaque" are more complex than initially proposed. We aimed to clarify whether plaque thrombogenicity is critical in atherothrombosis in mice. In a murine model of plaque destabilization, we enhanced plaque thrombogenicity by systemically overexpressing murine tissue factor (TF) by adenovirus-mediated gene transfer. The potential effects and mechanisms of TF on plaque destabilization were examined in cultured human aortic smooth muscle cells (HASMCs), RAW264...
November 27, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30500375/generation-of-directly-reprogrammed-human-endothelial-cells-derived-from-fibroblast-using-ultrasound
#11
Sung-Whan Kim, Hyun Aae Ryu, Yong Seung Lee, In Sil Jeong, Soonhag Kim
Physical microenvironment plays an important role in determining cellular reprogramming. In this study, we first generated directly reprogrammed human dermal fibroblasts (HDFs) into endothelial cells (ECs) mediated by environmental transition-guided cellular reprogramming (e/Entr) using ultrasound and characterized e/Entr. Ultrasound stimulus was introduced to ECs culture media and HDFs and induced into ECs-like cells. We performed microarray, RT-PCR, protein analysis, matrigel plug assay and e/Entr were transplanted into ischemic hindlimb mice model...
November 27, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30472253/cloning-and-characterization-of-zebrafish-k-2p-13-1-thik-1-two-pore-domain-k-channels
#12
Ingo Staudacher, Sebastian Seehausen, Jakob Gierten, Claudius Illg, Patrick A Schweizer, Hugo A Katus, Dierk Thomas
Two-pore-domain potassium (K2P ) channels conduct background potassium currents in the heart and other tissues. K2P currents are involved in the repolarization of action potentials and stabilize the resting membrane potential. Human K2P 13.1 (THIK-1) channels are expressed in the heart and have recently been implicated in atrial fibrillation. The in vivo significance of K2P 13.1 currents in cardiac electrophysiology is not known. We hypothesized that Danio rerio (zebrafish) may serve as model to elucidate the functional role of cardiac K2P 13...
November 22, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30472252/developing-potential-biomarkers-through-bedside-to-bench-translation
#13
EDITORIAL
D I Bromage, C X Santos, A M Shah
No abstract text is available yet for this article.
November 22, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30472251/early-inhibition-of-endothelial-retinoid-uptake-upon-myocardial-infarction-restores-cardiac-function-and-prevents-cell-tissue-and-animal-death
#14
Katarina Danzl, Barbara Messner, Christian Doppler, Clemens Nebert, Anna Abfalterer, Adel Sakic, Veronika Temml, Katharina Heinz, Robert Streitwieser, Thomas Edelmann, Mario Mairhofer, Michael Grimm, Günther Laufer, Andreas Zierer, Hermann Stuppner, Daniela Schuster, Christian Ploner, Thomas Müller, David Bernhard
Physiologically, following myocardial infarction (MI), retinoid levels elevate locally in the infarcted area. Whereas therapeutic systemic application of retinoids was shown to reduce the progression of ventricular dilatation and the onset of heart failure, the role of acute physiologically increased retinoids in the infarction zone is unknown to date. To reveal the role of local retinoids in the MI zone is the central aim of this study. Using human cell culture and co-culture models for hypoxia as well as various assays systems, lentivirus-based transgene expression, in silico molecular docking studies, and an MI model in rats, we analysed the impact of the retinoid all-trans retinoic acid (ATRA) on cell signalling, cell viability, tissue survival, heart function, and MI-induced death in rats...
November 22, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30465799/cathepsin-k-deficiency-impairs-mouse-cardiac-function-after-myocardial-infarction
#15
Wenqian Fang, Aina He, Mei-Xiang Xiang, Yan Lin, Yajun Wang, Jie Li, Chongzhe Yang, Xian Zhang, Cong-Lin Liu, Galina K Sukhova, Natasha Barascuk, Lise Larsen, Morten Karsdal, Peter Libby, Guo-Ping Shi
BACKGROUND: Extracellular matrix metabolism and cardiac cell death participate centrally in myocardial infarction (MI). This study tested the roles of collagenolytic cathepsin K (CatK) in post-MI left ventricular remodeling. METHODS AND RESULTS: Patients with acute MI had higher plasma CatK levels (20.49 ± 7.07 pmol/L, n = 26) than those in subjects with stable angina pectoris (8.34 ± 1.66 pmol/L, n = 28, P = .01) or those without coronary heart disease (6...
November 19, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30462989/kv4-3-expression-abrogates-and-reverses-norepinephrine-induced-myocyte-hypertrophy-by-camkii-inhibition
#16
Yanggan Wang, Thitima Keskanokwong, Jun Cheng
BACKGROUND: Down-regulation of Kv4.3 protein is a general feature of cardiac hypertrophy. Based on our recent studies, we propose that Kv4.3 reduction may be a hypertrophic stimulator. OBJECTIVE: We tested whether Kv4.3 expression can prevent or reverse cardiac hypertrophy induced by norepinephrine (NE). METHODS AND RESULTS: Incubation of 20 μM NE in cultured neonatal rat ventricular myocytes (NRVMs) for 48 h and 96 h induced myocyte hypertrophy in a time-dependent manner, characterized by progressive increase in cell size, protein/DNA ratio, ANP and BNP, along with an progressive increase in the activity of CaMKII and calcineurin and reduction of Kv4...
November 18, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30458169/from-pediatrics-to-geriatrics-mechanisms-of-heart-failure-across-the-life-course
#17
REVIEW
Kathleen C Woulfe, Danielle R Bruns
Heart failure (HF) is a significant public health problem and a disease with high 5-year mortality. Although age is the primary risk factor for development of HF, it is a disease which impacts patients of all ages. Historically, HF has been studied as a one-size fits all strategy- with the majority of both clinical and basic science investigations employing adult male subjects or adult male pre-clinical animal models. We postulate that inclusion of biological variables in HF studies is necessary to improve our understanding of mechanisms of HF and improve outcomes...
November 17, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30452906/flotillins-in-the-intercalated-disc-are-potential-modulators-of-cardiac-excitability
#18
Elise L Kessler, Leonie van Stuijvenberg, Joanne J A van Bavel, Joëlle van Bennekom, Anne Zwartsen, Mathilde R Rivaud, Aryan Vink, Igor R Efimov, Alex V Postma, J Peter van Tintelen, Carol A Remme, Marc A Vos, Antje Banning, Teun P de Boer, Ritva Tikkanen, Toon A B van Veen
BACKGROUND: The intercalated disc (ID) is important for cardiac remodeling and has become a subject of intensive research efforts. However, as yet the composition of the ID has still not been conclusively resolved and the role of many proteins identified in the ID, like Flotillin-2, is often unknown. The Flotillin proteins are known to be involved in the stabilization of cadherins and desmosomes in the epidermis and upon cancer development. However, their role in the heart has so far not been investigated...
November 16, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30448480/the-scffbxo3-ubiquitin-e3-ligase-regulates-inflammation-in-atherosclerosis
#19
Divay Chandra, James Londino, Shaun Alexander, Joseph S Bednash, Yingze Zhang, Robert M Friedlander, Grant Daskivich, Diane L Carlisle, William R Lariviere, Ana Carolina Igami Nakassa, Mark Ross, Claudette St Croix, Toru Nyunoya, Frank Sciurba, Bill Chen, Rama K Mallampalli
Inflammation is critical in the pathobiology of atherosclerosis. An essential player in the inflammatory process in atherosclerosis are macrophages that scavenge oxidatively modified low-density lipoproteins (OxLDL) deposited in the subendothelium of systemic arteries that secrete a myriad of pro-inflammatory mediators. Here, we identified that a subunit of the Skp-Cullin-F-box ubiquitin E3 ligase apparatus, termed FBXO3, modulates the inflammatory response in atherosclerosis. Specifically, individuals with a hypofunctioning genetic variant of FBXO3 develop less atherosclerosis...
November 16, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30448479/phosphorylation-of-cx43-residue-y313-by-src-contributes-to-blocking-the-interaction-with-drebrin-and-disassembling-gap-junctions
#20
Li Zheng, Hanjun Li, Andrew Cannon, Andrew J Trease, Gaelle Spagnol, Hong Zheng, Stanley Radio, Kaushik Patel, Surinder Batra, Paul L Sorgen
Phosphorylation regulates connexin43 (Cx43) function from assembly/disassembly to coupling at the plaque. Src is a tyrosine kinase known to both phosphorylate Cx43 (residues Y247 and Y265) and affect gap junction intercellular communication. However, the Cx43 carboxyl-terminal (CT) domain contains additional tyrosine residues and proteomic discovery mass spectrometry data identified Y313 as a potential phosphorylation target. Based upon the study of Lin et al. (2001) J. Cell Biol., which still observed tyrosine phosphorylation by Src when using a Cx43 Y247/Y265F mutant, we addressed the possibility of Y313 phosphorylation (pY313) by Src...
November 15, 2018: Journal of Molecular and Cellular Cardiology
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