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https://www.readbyqxmd.com/read/29317051/the-end-stage-failing-human-myocardium-where-changes-in-ultrastructure-of-human-cardiac-muscle-cells-do-not-appear-to-dictate-clinical-outcomes
#1
Ivan Varga, Paulina Galfiova, Andrea Gazova, Tomas Barczi, Stefan Polak, Lubos Danisovic, Michal Hulman, Jan Kyselovic
Heart failure is the end stage of cardiovascular abnormalities. Studies have primarily focused on the functional changes of cardiomyocytes in the failing heart from different animal models with very little information in the human condition. In addition little is known about the ultrastructural changes that proceed in cardiomyocytes in route to failure. The aim of this study was to examine the ultrastructural changes in the myocardium of human with end-stage heart failure. Left ventricular myocardial tissue samples from 7 patients with end-stage heart failure were examined with transmission and scanning electron microscopy...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29306897/critical-roles-of-xirp-proteins-in-cardiac-conduction-and-their-rare-variants-identified-in-sudden-unexplained-nocturnal-death-syndrome-and-brugada-syndrome-in-chinese-han-population
#2
Lei Huang, Kuo-Ho Wu, Liyong Zhang, Qinchuan Wang, Shuangbo Tang, Qiuping Wu, Pei-Hsiu Jiang, Jim Jung-Ching Lin, Jian Guo, Lin Wang, Shih-Hurng Loh, Jianding Cheng
BACKGROUND: Sudden unexplained nocturnal death syndrome (SUNDS) remains an autopsy negative entity with unclear etiology. Arrhythmia has been implicated in SUNDS. Mutations/deficiencies in intercalated disc components have been shown to cause arrhythmias. Human cardiomyopathy-associated 1 (XIRP1) and 3 (XIRP2) are intercalated disc-associated, Xin repeats-containing proteins. Mouse Xirp1 is necessary for the integrity of intercalated disc and for the surface expression of transient outward and delayed rectifier K+ channels, whereas mouse Xirp2 is required for Xirp1 intercalated disc localization...
January 6, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29222390/sodium-channel-remodeling-in-subcellular-microdomains-of-murine-failing-cardiomyocytes
#3
Mathilde R Rivaud, Esperanza Agullo-Pascual, Xianming Lin, Alejandra Leo-Macias, Mingliang Zhang, Eli Rothenberg, Connie R Bezzina, Mario Delmar, Carol Ann Remme
BACKGROUND: Cardiac sodium channel (NaV1.5) dysfunction contributes to arrhythmogenesis during pathophysiological conditions. Nav1.5 localizes to distinct subcellular microdomains within the cardiomyocyte, where it associates with region-specific proteins, yielding complexes whose function is location specific. We herein investigated sodium channel remodeling within distinct cardiomyocyte microdomains during heart failure. METHODS AND RESULTS: Mice were subjected to 6 weeks of transverse aortic constriction (TAC; n=32) to induce heart failure...
December 8, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29212896/the-novel-desmin-mutation-p-glu401asp-impairs-filament-formation-disrupts-cell-membrane-integrity-and-causes-severe-arrhythmogenic-left-ventricular-cardiomyopathy-dysplasia
#4
Francisco José Bermúdez-Jiménez, Víctor Carriel, Andreas Brodehl, Miguel Alaminos, Antonio Campos, Ilona Schirmer, Hendrik Milting, Beatriz Álvarez Abril, Miguel Álvarez, Silvia López-Fernández, Diego García-Giustiniani, Lorenzo Monserrat, Luis Tercedor, Juan Jiménez-Jáimez
Background -Desmin (DES) mutations cause severe skeletal and cardiac muscle disease with heterogeneous phenotypes. Recently, DES mutations were described in patients with inherited arrhythmogenic right ventricular cardiomyopathy/dysplasia (iARVC/D), although their cellular and molecular pathomechanisms are not precisely known. Our aim is to describe clinically and functionally the novel DES-p.Glu401Asp mutation as a cause of inherited left ventricular arrhythmogenic cardiomyopathy/dysplasia (iLVAC/D). Methods -We identified the novel DES mutation p...
December 6, 2017: Circulation
https://www.readbyqxmd.com/read/29210458/distribution-of-cardiac-sodium-channels-in-clusters-potentiates-ephaptic-interactions-in-the-intercalated-disc
#5
Echrak Hichri, Hugues Abriel, Jan P Kucera
It has been proposed that ephaptic interactions in intercalated discs, mediated by extracellular potentials, contribute to cardiac impulse propagation when gap junctional coupling is reduced. However, experiments demonstrating ephaptic effects on the cardiac Na+ current (INa ) are scarce. Furthermore, Na+ channels form clusters around gap junction plaques, but the electrophysiological significance of these clusters has never been investigated. In patch clamp experiments with HEK cells stably expressing human Nav 1...
December 6, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29176328/cardiomyopathy-associated-gene-1-sensitive-pkc-dependent-connexin-43-expression-and-phosphorylation-in-left-ventricular-noncompaction-cardiomyopathy
#6
Yuanyuan Xie, Shenghua Liu, Shengshou Hu, Yingjie Wei
BACKGROUND/AIMS: Cardiomyopathy-associated gene 1 (CMYA1) plays an important role in embryonic cardiac development, postnatal cardiac remodeling and myocardial injury repair. Abnormal CMYA1 expression may be involved in cardiac dysplasia and primary cardiomyopathy. Our study aims to establish the relationship between CMYA1 and Left ventricular noncompaction cardiomyopathy (LVNC) pathogenesis. METHODS: We explored the effects of CMYA1 on connexins (Cx), which contribute to gap junction intercellular communication (GJIC), and the underlying signaling pathway in human normal tissues, LVNC myocardial tissues and HL1 cells by means of western blotting, RT-qPCR, immunohistochemistry, immunofluorescence, co-immunoprecipitation and scrape loading-dye transfer...
November 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29101288/increased-cardiac-arrhythmogenesis-associated-with-gap-junction-remodeling-with-upregulation-of-rna-binding-protein-fxr1
#7
Miensheng Chu, Stefanie Mares Novak, Cathleen Cover, Anne A Wang, Ikeotunye Royal Chinyere, Elizabeth Juneman, Daniela C Zarnescu, Pak Kin Wong, Carol Gregorio
Background -Gap junction remodeling is well established as a consistent feature of human heart disease involving spontaneous ventricular arrhythmia. The mechanisms responsible for gap junction remodeling that include alterations in the distribution of, and protein expression within, gap junctions are still debated. Studies reveal that multiple transcriptional and post-transcriptional regulatory pathways are triggered in response to cardiac disease, such as those involving RNA-binding proteins. The expression levels of Fragile X mental retardation autosomal homolog 1 (FXR1), an RNA-binding protein, are critical to maintain proper cardiac muscle function; however, the connection between FXR1 and disease is not clear...
November 3, 2017: Circulation
https://www.readbyqxmd.com/read/29016731/electrical-coupling-between-ventricular-myocytes-and-myofibroblasts-in-the-infarcted-mouse-heart
#8
Michael Rubart, Wen Tao, Xiao-Long Lu, Simon J Conway, Sean P Reuter, Shien-Fong Lin, Mark H Soonpaa
Aims: Recent studies have demonstrated electrotonic coupling between scar tissue and the surrounding myocardium in cryoinjured hearts. However, the electrical dynamics occurring at the myocyte-nonmyocyte interface in the fibrotic heart remain undefined. Here, we sought to develop an assay to interrogate the nonmyocyte cell type contributing to heterocellular coupling and to characterize, on a cellular scale, its voltage response in the infarct border zone of living hearts. Methods and results: We used two-photon laser scanning microscopy in conjunction with a voltage-sensitive dye to record transmembrane voltage changes simultaneously from cardiomyocytes and adjoined nonmyocytes in Langendorff-perfused mouse hearts with healing myocardial infarction...
September 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28982073/cardiac-specific-inactivation-of-lpp3-in-mice-leads-to-myocardial-dysfunction-and-heart-failure
#9
Mini Chandra, Diana Escalante-Alcalde, Md Shenuarin Bhuiyan, Anthony Wayne Orr, Christopher Kevil, Andrew J Morris, Hyung Nam, Paari Dominic, Kevin J McCarthy, Sumitra Miriyala, Manikandan Panchatcharam
Lipid Phosphate phosphatase 3 (LPP3), encoded by the Plpp3 gene, is an enzyme that dephosphorylates the bioactive lipid mediator lysophosphatidic acid (LPA). To study the role of LPP3 in the myocardium, we generated a cardiac specific Plpp3 deficient mouse strain. Although these mice were viable at birth in contrast to global Plpp3 knockout mice, they showed increased mortality ~ 8 months. LPP3 deficient mice had enlarged hearts with reduced left ventricular performance as seen by echocardiography. Cardiac specific Plpp3 deficient mice had longer ventricular effective refractory periods compared to their Plpp3 littermates...
September 28, 2017: Redox Biology
https://www.readbyqxmd.com/read/28957532/arrhythmogenic-cardiomyopathy-pathology-genetics-and-concepts-in-pathogenesis
#10
Edgar T Hoorntje, Wouter P Te Rijdt, Cynthia A James, Kalliopi Pilichou, Cristina Basso, Daniel P Judge, Connie R Bezzina, J Peter van Tintelen
Arrhythmogenic cardiomyopathy (ACM) is a rare, heritable heart disease characterized by fibro-fatty replacement of the myocardium and a high degree of electric instability. It was first thought to be a congenital disorder, but is now regarded as a dystrophic heart muscle disease that develops over time. There is no curative treatment and current treatment strategies focus on attenuating the symptoms, slowing disease progression, and preventing life-threatening arrhythmias and sudden cardiac death. Identification of mutations in genes encoding desmosomal proteins and in other genes has led to insights into the disease pathogenesis and greatly facilitated identification of family members at risk...
October 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28948000/wnt-%C3%AE-catenin-pathway-in-arrhythmogenic-cardiomyopathy
#11
REVIEW
Alessandra Lorenzon, Martina Calore, Giulia Poloni, Leon J De Windt, Paola Braghetta, Alessandra Rampazzo
Wnt/β-catenin signaling pathway plays essential roles in heart development as well as cardiac tissue homoeostasis in adults. Abnormal regulation of this signaling pathway is linked to a variety of cardiac disease conditions, including hypertrophy, fibrosis, arrhythmias, and infarction. Recent studies on genetically modified cellular and animal models document a crucial role of Wnt/β-catenin signaling in the molecular pathogenesis of arrhythmogenic cardiomyopathy (AC), an inherited disease of intercalated discs, typically characterized by ventricular arrhythmias and progressive substitution of the myocardium with fibrofatty tissue...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28934278/intercalated-disc-in-failing-hearts-from-patients-with-dilated-cardiomyopathy-its-role-in-the-depressed-left-ventricular-function
#12
Ana Ortega, Estefanía Tarazón, Carolina Gil-Cayuela, María García-Manzanares, Luis Martínez-Dolz, Francisca Lago, José Ramón González-Juanatey, Juan Cinca, Esther Jorge, Manuel Portolés, Esther Roselló-Lletí, Miguel Rivera
Alterations in myocardial structure and reduced cardiomyocyte adhesions have been previously described in dilated cardiomyopathy (DCM). We studied the transcriptome of cell adhesion molecules in these patients and their relationships with left ventricular (LV) function decay. We also visualized the intercalated disc (ID) structure and organization. The transcriptomic profile of 23 explanted LV samples was analyzed using RNA-sequencing (13 DCM, 10 control [CNT]), focusing on cell adhesion genes. Electron microscopy analysis to visualize ID structural differences and immunohistochemistry experiments of ID proteins was also performed...
2017: PloS One
https://www.readbyqxmd.com/read/28923791/gja1-20k-arranges-actin-to-guide-cx43-delivery-to-cardiac-intercalated-discs
#13
Wassim A Basheer, Shaohua Xiao, Irina Epifantseva, Ying Fu, Andre G Kleber, TingTing Hong, Robin M Shaw
RATIONALE: Delivery of Cx43 (connexin 43) to the intercalated disc is a continuous and rapid process critical for intercellular coupling. By a pathway of targeted delivery involving microtubule highways, vesicles of Cx43 hemichannels are efficiently trafficked to adherens junctions at intercalated discs. It has also been identified that actin provides rest stops for Cx43 forward trafficking and that Cx43 has a 20 kDa internally translated small C terminus isoform, GJA1-20k (Gap Junction Protein Alpha 1- 20 kDa), which is required for full-length Cx43 trafficking, but by an unknown mechanism...
October 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/28870505/tgf-%C3%AE-1-affects-cell-cell-adhesion-in-the-heart-in-an-ncam1-dependent-mechanism
#14
Maegen A Ackermann, Jennifer M Petrosino, Heather R Manring, Patrick Wright, Vikram Shettigar, Ahmet Kilic, Paul M L Janssen, Mark T Ziolo, Federica Accornero
The contractile property of the myocardium is maintained by cell-cell junctions enabling cardiomyocytes to work as a syncytium. Alterations in cell-cell junctions are observed in heart failure, a disease characterized by the activation of Transforming Growth Factor beta 1 (TGFβ1). While TGFβ1 has been implicated in diverse biologic responses, its molecular function in controlling cell-cell adhesion in the heart has never been investigated. Cardiac-specific transgenic mice expressing active TGFβ1 were generated to model the observed increase in activity in the failing heart...
November 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28841299/cellulose-organic-montmorillonite-nanocomposites-as-biomacromolecular-quorum-sensing-inhibitor
#15
Deniz Demircan, Sedef Ilk, Baozhong Zhang
The aim of this study was to develop simple cellulose nanocomposites that can interfere with the quorum-sensing (QS)-regulated physiological process of bacteria, which will provide a sustainable and inexpensive solution to the serious challenges caused by bacterial infections in various products like food packaging or biomedical materials. Three cellulose nanocomposites with 1-5 w% octadecylamine-modified montmorillonite (ODA-MMT) were prepared by regeneration of cellulose from ionic liquid solutions in the presence of ODA-MMT suspension...
September 6, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28827800/hspb7-prevents-cardiac-conduction-system-defect-through-maintaining-intercalated-disc-integrity
#16
Wern-Chir Liao, Liang-Yi Juo, Yen-Ling Shih, Yen-Hui Chen, Yu-Ting Yan
HSPB7 is a member of the small heat-shock protein (HSPB) family and is expressed in the cardiomyocytes from cardiogenesis onwards. A dramatic increase in HSPB7 is detected in the heart and blood plasma immediately after myocardial infarction. Additionally, several single-nucleotide polymorphisms of HSPB7 have been identified to be associated with heart failure caused by cardiomyopathy in human patients. Although a recent study has shown that HSPB7 is required for maintaining myofiber structure in skeletal muscle, its molecular and physiological functions in the heart remain unclear...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28826662/novel-obscurins-mediate-cardiomyocyte-adhesion-and-size-via-the-pi3k-akt-mtor-signaling-pathway
#17
Maegen A Ackermann, Brendan King, Nicole A P Lieberman, Prameela J Bobbili, Michael Rudloff, Christopher E Berndsen, Nathan T Wright, Peter A Hecker, Aikaterini Kontrogianni-Konstantopoulos
The intercalated disc of cardiac muscle embodies a highly-ordered, multifunctional network, essential for the synchronous contraction of the heart. Over 200 known proteins localize to the intercalated disc. The challenge now lies in their characterization as it relates to the coupling of neighboring cells and whole heart function. Using molecular, biochemical and imaging techniques, we characterized for the first time two small obscurin isoforms, obscurin-40 and obscurin-80, which are enriched at distinct locations of the intercalated disc...
October 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28792844/trpa1-ion-channel-stimulation-enhances-cardiomyocyte-contractile-function-via-a-camkii-dependent-pathway
#18
Spencer R Andrei, Monica Ghosh, Pritam Sinharoy, Souvik Dey, Ian N Bratz, Derek S Damron
RATIONALE: Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation channels that show high permeability to calcium. Previous studies from our laboratory have demonstrated that TRPA1 ion channels are expressed in adult mouse ventricular cardiomyocytes (CMs) and are localized at the z-disk, costamere and intercalated disk. The functional significance of TRPA1 ion channels in the modulation of CM contractile function have not been explored. OBJECTIVE: To identify the extent to which TRPA1 ion channels are involved in modulating CM contractile function and elucidate the cellular mechanism of action...
August 9, 2017: Channels
https://www.readbyqxmd.com/read/28764973/disturbed-desmoglein-2-in-the-intercalated-disc-of-pediatric-patients-with-dilated-cardiomyopathy
#19
Elise L Kessler, Peter Gj Nikkels, Toon Ab van Veen
Dilated cardiomyopathy (DCM) leads to disturbed contraction and force transduction, and is associated with substantial mortality in all age groups. Involvement of a disrupted composition of the intercalated disc (ID) has been reported. However, in children, little is established about such subcellular changes during disease, because of the pathological mix-up with the ongoing cardiac maturation. This leaves maladaptive remodeling often undetected. We aimed at illustrating subcellular alterations in children diagnosed with DCM compared to age-matched controls, focusing on ID proteins known to be crucially stable under healthy conditions and destabilized during cardiac injury in adults...
September 2017: Human Pathology
https://www.readbyqxmd.com/read/28762141/anti-fibronectin-aptamers-improve-the-colonization-of-chitosan-films-modified-with-d-raffinose-by-murine-osteoblastic-cells
#20
L Parisi, C Galli, A Bianchera, P Lagonegro, L Elviri, A Smerieri, S Lumetti, E Manfredi, R Bettini, G M Macaluso
The aim of the present study was to investigate how the enrichment of chitosan films with anti-fibronectin aptamers could enhance scaffold colonization by osteoblasts, by improving their adhesion and accelerating their proliferation. Chitosan discs were enriched with excess of anti-fibronectin aptamer. Aptamer adsorption on chitosan was monitored by measuring aptamer concentration in the supernatant by spectrophotometry, as well as its release, while functionalization was confirmed by labelling aptamers with a DNA intercalating dye...
September 2017: Journal of Materials Science. Materials in Medicine
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