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Journal of Molecular and Cellular Cardiology

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https://www.readbyqxmd.com/read/28803858/in-silico-investigations-of-the-functional-impact-of-kcna5-mutations-on-atrial-mechanical-dynamics
#1
Haibo Ni, Ismail Adeniran, Henggui Zhang
A recent study has identified six novel genetic variations (D322H, E48G, A305T, D469E, Y155C, P488S) in KCNA5 (encoding Kv1.5 which carries the atrial-specific ultra-rapid delayed rectifier current, IKur) in patients with early onset of lone atrial fibrillation. These mutations are distinctive, resulting in either gain-of-function (D322H, E48G, A305T) or loss-of-function (D469E, Y155C, P488S) of IKur channels. Though affecting potassium channels, they may modulate the cellular active force and therefore atrial mechanical functions, which remains to be elucidated...
August 10, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28782514/exosomes-as-agents-of-change-in-the-cardiovascular-system
#2
REVIEW
A J Poe, A A Knowlton
Exosomes have an evolving role in paracrine and autocrine signaling, which is enhanced because these lipid vesicles are quite stable and can deliver miRNA, DNA, protein and other molecules to cells throughout the body. Most cell types release exosomes, and exosomes are found in all biological fluids, making them accessible biomarkers. Significantly, exosomes can carry a biologically potent cargo, which can alter the phenotype of recipient cells. In the cardiovascular system exosomes have been primarily studied for their role in mediating the beneficial effects of mesenchymal stem cells after myocardial injury...
August 3, 2017: Journal of Molecular and Cellular Cardiology
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
#3
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/28778766/the-impact-of-ovariectomy-on-cardiac-excitation-contraction-coupling-is-mediated-through-camp-pka-dependent-mechanisms
#4
Randi J Parks, Oleg Bogachev, Martin Mackasey, Gibanananda Ray, Robert A Rose, Susan E Howlett
Ovariectomy (OVX) promotes sarcoplasmic reticulum (SR) Ca(2+) overload in ventricular myocytes. We hypothesized that the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway contributes to this Ca(2+) dysregulation. Myocytes were isolated from adult female C57BL/6 mice following either OVX or sham surgery (surgery at ≈1mos). Contractions, Ca(2+) concentrations (fura-2) and ionic currents were measured simultaneously (37°C, 2Hz) in voltage-clamped myocytes. Intracellular cAMP levels were determined with an enzyme immunoassay; phosphodiesterase (PDE) and adenylyl cyclase (AC) isoform expression was examined with qPCR...
August 1, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28778765/beta-adrenergic-regulation-of-the-heart-expressing-the-ser1700a-thr1704a-mutated-cav1-2-channel
#5
Montatip Poomvanicha, Jan Matthes, Katrin Domes, Enrico Patrucco, Elisabeth Angermeier, Karl-Ludwig Laugwitz, Toni Schneider, Franz Hofmann
Beta-adrenergic stimulation of the heart increases ICa. PKA dependent phosphorylation of several amino acids (among them Ser 1700 and Thr 1704 in the carboxy-terminus of the Cav1.2 α1c subunit) has been implicated as decisive for the β-adrenergic up-regulation of cardiac ICa. Mutation of Ser 1700 and Thr 1704 to alanine results in the Cav1.2PKA_P2(-/-) mice. Cav1.2PKA_P2(-/-) mice display reduced cardiac L-type current. Fractional shortening and ejection fraction in the intact animal and ICa in isolated cardiomyocytes (CM) are stimulated by isoproterenol...
August 1, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28760564/junctional-delay-frequency-and-direction-dependent-uncoupling-of-human-heterotypic-cx45-cx43-gap-junction-channels
#6
Willy G Ye, Benny Yue, Hiroshi Aoyama, Nicholas K Kim, John A Cameron, Honghong Chen, Donglin Bai
Gap junction (GJ) channels form low resistance passages between cardiomyocytes and play a role in the rapid propagation of action potentials in the heart. A GJ channel is formed by two properly docked hemichannels and each hemichannel is a hexamer of connexins. Connexin40 (Cx40) and Cx43 are the dominant connexins in atrial myocytes, while Cx45 is mostly expressed in the sinoatrial (SA) and atrioventricular (AV) nodes which directly connect nodal cells with atrial myocytes, possibly via heterotypic Cx40/Cx45 and/or Cx43/Cx45 GJs...
July 29, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28757442/endothelin-receptor-mediated-ca-2-signaling-in-coronary-arteries-after-experimentally-induced-ischemia-reperfusion-injury-in-rat
#7
Sarah Brøgger Kristiansen, Kristian A Haanes, Majid Sheykhzade, Lars Edvinsson
BACKGROUND: Acute myocardial infarction is one of the leading causes of death. It is caused by a blockage of a coronary artery leading to reduced blood flow to the myocardium and hence ischemic damage. In addition, a second wave of damage after the flow has been restored, named reperfusion injury greatly exacerbate the damage. For the latter, no medical treatment exist. In this study the aim was to characterize Ca(2+) sensitivity in coronary arteries following experimental ischemia/reperfusion injury...
July 27, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28756206/entanglement-of-gsk-3%C3%AE-%C3%AE-catenin-and-tgf-%C3%AE-1-signaling-network-to-regulate-myocardial-fibrosis
#8
REVIEW
Yuanjun Guo, Manisha Gupte, Prachi Umbarkar, Anand Prakash Singh, Jennifer Y Sui, Thomas Force, Hind Lal
Nearly every form of the heart disease is associated with myocardial fibrosis, which is characterized by the accumulation of activated cardiac fibroblasts (CFs) and excess deposition of extracellular matrix (ECM). Although, CFs are the primary mediators of myocardial fibrosis in a diseased heart, in the traditional view, activated CFs (myofibroblasts) and resulting fibrosis were simply considered the secondary consequence of the disease, not the cause. Recent studies from our lab and others have challenged this concept by demonstrating that fibroblast activation and fibrosis are not simply the secondary consequence of a diseased heart, but are crucial for mediating various myocardial disease processes...
July 27, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28754342/intramolecular-signaling-in-a-cardiac-connexin-role-of-cytoplasmic-domain-dimerization
#9
Andrew J Trease, Juan M V Capuccino, Jorge Contreras, Andrew L Harris, Paul L Sorgen
Gap junctions, composed of connexins, mediate electrical coupling and impulse propagation in the working myocardium. In the human heart, the spatio-temporal regulation and distinct functional properties of the three dominant connexins (Cx43, Cx45, and Cx40) suggests non-redundant physiological roles for each isoform. There are substantial differences in gating properties, expression, and trafficking among these isoforms, however, little is known about the determinants of these different phenotypes. To gain insight regarding these determinants, we focused on the carboxyl-terminal (CT) domain because of its importance in channel regulation and large degree of sequence divergence among connexin family members...
July 25, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28739325/d242n-a-kv7-1-lqts-mutation-uncovers-a-key-residue-for-iks-voltage-dependence
#10
Cristina Moreno, Anna Oliveras, Chiara Bartolucci, Carmen Muñoz, Alicia de la Cruz, Diego A Peraza, Juan R Gimeno, Mercedes Martín-Martínez, Stefano Severi, Antonio Felipe, Pier D Lambiase, Teresa Gonzalez, Carmen Valenzuela
KV7.1 and KCNE1 co-assemble to give rise to the IKs current, one of the most important repolarizing currents of the cardiac action potential. Its relevance is underscored by the identification of >500 mutations in KV7.1 and, at least, 36 in KCNE1, that cause Long QT Syndrome (LQTS). The aim of this study was to characterize the biophysical and cellular consequences of the D242N KV7.1 mutation associated with the LQTS. The mutation is located in the S4 transmembrane segment, within the voltage sensor of the KV7...
July 22, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28739324/reaction-based-small-molecule-fluorescent-probes-for-dynamic-detection-of-ros-and-transient-redox-changes-in-living-cells-and-small-animals
#11
REVIEW
Rui Lü
Dynamic detection of transient redox changes in living cells and animals has broad implications for human health and disease diagnosis, because intracellular redox homeostasis regulated by reactive oxygen species (ROS) plays important role in cell functions, normal physiological functions and some serious human diseases (e.g., cancer, Alzheimer's disease, diabetes, etc.) usually have close relationship with the intracellular redox status. Small-molecule ROS-responsive fluorescent probes can act as powerful tools for dynamic detection of ROS and redox changes in living cells and animals through fluorescence imaging techniques; and great advances have been achieved recently in the design and synthesis of small-molecule ROS-responsive fluorescent probes...
July 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28736262/bdnf-a-key-player-in-cardiovascular-system
#12
REVIEW
Ewa Pius-Sadowska, Bogusław Machaliński
Neurotrophins (NTs) were first identified as target-derived survival factors for neurons of the central and peripheral nervous system (PNS). They are known to control neural cell fate, development and function. Independently of their neuronal properties, NTs exert unique cardiovascular activity. The heart is innervated by sensory, sympathetic and parasympathetic neurons, which require NTs during early development and in the establishment of mature properties, contributing to the maintenance of cardiovascular homeostasis...
July 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28736261/genetic-disruption-of-the-cardiomyocyte-circadian-clock-differentially-influences-insulin-mediated-processes-in-the-heart
#13
Graham R McGinnis, Yawen Tang, Rachel A Brewer, Manoja K Brahma, Haley L Stanley, Gobinath Shanmugam, Namakkal Soorappan Rajasekaran, Glenn C Rowe, Stuart J Frank, Adam R Wende, E Dale Abel, Heinrich Taegtmeyer, Silvio Litovsky, Victor Darley-Usmar, Jianhua Zhang, John C Chatham, Martin E Young
Cardiovascular physiology exhibits time-of-day-dependent oscillations, which are mediated by both extrinsic (e.g., environment/behavior) and intrinsic (e.g., circadian clock) factors. Disruption of circadian rhythms negatively affects multiple cardiometabolic parameters. Recent studies suggest that the cardiomyocyte circadian clock directly modulates responsiveness of the heart to metabolic stimuli (e.g., fatty acids) and stresses (e.g., ischemia/reperfusion). The aim of this study was to determine whether genetic disruption of the cardiomyocyte circadian clock impacts insulin-regulated pathways in the heart...
July 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28736260/soluble-epoxide-hydrolase-activation-by-s-nitrosation-contributes-to-cardiac-ischemia-reperfusion-injury
#14
Yuzhu Ding, Yazi Li, Xu Zhang, Jinlong He, Dong Lu, Xuan Fang, Yuchen Wang, Jiaxing Wang, Yuying Zhang, Xinhua Qiao, Li-Ming Gan, Chang Chen, Yi Zhu
Cardiac ischemia-reperfusion (I/R) injury always accompanies recanalization treatment for myocardial infarction. Here we found soluble epoxide hydrolase (sEH), which metabolizes cardioprotective epoxyeicosatrienoic acids into less effective diols, was rapidly activated during myocardial reperfusion in both mouse and rat models in expression-independent manner. Similar activation was mimicked by nitric oxide (NO) donor dose-dependently in vitro, along with an obvious induction of sEH S-nitrosation, a short-term post-translational modification, which diminished in sEH Cys-141-Ala mutant...
July 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28709768/plasma-sphingosine-1-phosphate-concentrations-are-associated-with-systolic-heart-failure-in-patients-with-ischemic-heart-disease
#15
Amin Polzin, Kerstin Piayda, Petra Keul, Lisa Dannenberg, Annemarie Mohring, Markus Gräler, Tobias Zeus, Malte Kelm, Bodo Levkau
OBJECTIVE: Sphingosine-1-Phosphate (S1P) is a bioactive sphingolipid with important functions in immunity, inflammation and cardiovascular biology. S1P is associated with prevalence and severity of coronary artery disease and myocardial infarction. However, its relevance in ischemic cardiomyopathy is unknown. We aimed to investigate associations of plasma S1P and other sphingolipids with the extent of heart failure in patients with ischemic heart disease. METHODS AND RESULTS: 74 patients with ischemic heart disease were investigated in this observational study...
July 12, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28709769/exploring-the-mitochondrial-microrna-import-pathway-through-polynucleotide-phosphorylase-pnpase
#16
Danielle L Shepherd, Quincy A Hathaway, Mark V Pinti, Cody E Nichols, Andrya J Durr, Shruthi Sreekumar, Kristen M Hughes, Seth M Stine, Ivan Martinez, John M Hollander
Cardiovascular disease is the primary cause of mortality for individuals with type 2 diabetes mellitus. During the diabetic condition, cardiovascular dysfunction can be partially attributed to molecular changes in the tissue, including alterations in microRNA (miRNA) interactions. MiRNAs have been reported in the mitochondrion and their presence may influence cellular bioenergetics, creating decrements in functional capacity. In this study, we examined the roles of Argonaute 2 (Ago2), a protein associated with cytosolic and mitochondrial miRNAs, and Polynucleotide Phosphorylase (PNPase), a protein found in the inner membrane space of the mitochondrion, to determine their role in mitochondrial miRNA import...
July 11, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28705612/cardiac-mitochondrial-dynamics-mir-mediated-regulation-during-cardiac-injury
#17
Anusha Sivakumar, Ramasamy Subbiah, Rekha Balakrishnan, Jeyaprakash Rajendhran
Mitochondrial integrity is indispensable for cardiac health. With the advent of modern imaging technologies, mitochondrial motility and dynamics within the cell are extensively studied. Terminally differentiated and well-structured cardiomyocytes depict little mitochondrial division and fusion, questioning the contribution of mitochondrial fusion proteins (Mitofusin 1/2 and Optic Atrophy 1 protein) and fission factors (Dynamin-like protein 1 and mitochondrial fission 1 protein) in cardiomyocyte homeostasis...
July 10, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28689005/neuregulin-1%C3%AE-as-a-potential-therapeutic-for-targeting-fibroblasts-in-heart-disease
#18
EDITORIAL
Jason D Gardner
No abstract text is available yet for this article.
July 5, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28689004/the-role-of-succinate-and-ros-in-reperfusion-injury-a-critical-appraisal
#19
REVIEW
Tatyana N Andrienko, Philippe Pasdois, Gonçalo C Pereira, Matthew J Ovens, Andrew P Halestrap
We critically assess the proposal that succinate-fuelled reverse electron flow (REF) drives mitochondrial matrix superoxide production from Complex I early in reperfusion, thus acting as a key mediator of ischemia/reperfusion (IR) injury. Real-time surface fluorescence measurements of NAD(P)H and flavoprotein redox state suggest that conditions are unfavourable for REF during early reperfusion. Furthermore, rapid loss of succinate accumulated during ischemia can be explained by its efflux rather than oxidation...
July 5, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28684310/selective-inhibition-of-plasma-membrane-calcium-atpase-4-improves-angiogenesis-and-vascular-reperfusion
#20
Sathishkumar Kurusamy, Dolores López-Maderuelo, Robert Little, David Cadagan, Aaron M Savage, Jude C Ihugba, Rhiannon R Baggott, Farjana B Rowther, Sara Martínez-Martínez, Pablo Gómez-Del Arco, Clare Murcott, Weiguang Wang, J Francisco Nistal, Delvac Oceandy, Ludwig Neyses, Robert N Wilkinson, Elizabeth J Cartwright, Juan Miguel Redondo, Angel Luis Armesilla
AIMS: Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of ischaemic tissues in patients. Failure to restore efficient VEGF activity in the ischaemic organ remains a major problem in current pro-angiogenic therapeutic approaches. Plasma membrane calcium ATPase 4 (PMCA4) negatively regulates VEGF-activated angiogenesis via inhibition of the calcineurin/NFAT signalling pathway...
July 3, 2017: Journal of Molecular and Cellular Cardiology
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