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https://www.readbyqxmd.com/read/29101288/increased-cardiac-arrhythmogenesis-associated-with-gap-junction-remodeling-with-upregulation-of-rna-binding-protein-fxr1
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28735524/characterization-of-cytoskeleton-features-and-maturation-status-of-cultured-human-ipsc-derived-cardiomyocytes
#15
Christian Zuppinger, George Gibbons, Priyanka Dutta-Passecker, Adrian Segiser, Henriette Most, Thomas M Suter
Recent innovations in stem cell technologies and the availability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have opened new possibilities for studies and drug testing on human cardiomyocytes in vitro. Still, there are concerns about the precise nature of such 'reprogrammed' cells. We have performed an investigation using immunocytochemistry and confocal microscopy on several cellular features using commercially available hiPSC-CMs. For some selected developmentally regulated or cardiac chamber-specific proteins, we have compared the results from hiPSC-derived cardiomyocytes with freshly isolated, ventricular cardiomyocytes from adult rats...
June 21, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28716666/mouse-cardiac-mitochondria-do-not-separate-in-subsarcolemmal-and-interfibrillar-subpopulations
#16
Ulrike B Hendgen-Cotta, Sonja Esfeld, Holger Jastrow, Matthias Totzeck, Joachim Altschmied, Christine Goy, Judith Haendeler, Elke Winterhager, Tienush Rassaf
Cardiomyocytes consist of longitudinally oriented myofibril bundles with a misaligned composition caused by the uneven contours of the intercalated discs. The cytoplasmic space harbors the organelles, including mitochondria. This study investigated whether cardiomyocytes contain spatially and ultrastructurally discrete pools of mitochondria that can be separated for structurally and functionally appraisal in (patho)physiology. Transmission electron microscopy disclosed continuous transitions of mitochondria without attributable characteristics from beneath the sarcolemma directly into the barrier-free cytoplasmic space between myofibrils...
July 14, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28703223/unmasking-the-molecular-link-between-arrhythmogenic-cardiomyopathy-and-brugada-syndrome
#17
REVIEW
Javier Moncayo-Arlandi, Ramon Brugada
The intercalated discs that connect cardiomyocytes control cell-to-cell adhesion and communication. Several macromolecular structures (desmosomes, fascia adherens junctions, gap junctions, and sodium-channel complexes) coexist in, and confer their mechanical and electrical properties to, the intercalated disc. Traditionally, each structure was assumed to have a unique function in the intercalated disc. However, growing evidence suggests that these complexes act together in intercellular communication and adhesion, forming a single structural and functional entity - the connexome...
July 13, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28640448/overview-of-the-muscle-cytoskeleton
#18
Christine A Henderson, Christopher G Gomez, Stefanie M Novak, Lei Mi-Mi, Carol C Gregorio
Cardiac and skeletal striated muscles are intricately designed machines responsible for muscle contraction. Coordination of the basic contractile unit, the sarcomere, and the complex cytoskeletal networks are critical for contractile activity. The sarcomere is comprised of precisely organized individual filament systems that include thin (actin), thick (myosin), titin, and nebulin. Connecting the sarcomere to other organelles (e.g., mitochondria and nucleus) and serving as the scaffold to maintain cellular integrity are the intermediate filaments...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28578331/whole-genome-sequence-identified-a-rare-homozygous-pathogenic-mutation-of-the-dsg2-gene-in-a-familial-arrhythmogenic-cardiomyopathy-involving-both-ventricles
#19
Yubi Lin, Qianhuan Zhang, Zhi An Zhong, Zhe Xu, Siqi He, Fang Rao, Yang Liu, Jiaojiao Tang, Feng Wang, Hui Liu, Jiajun Xie, Hongmei Wu, Shuxia Wang, Xin Li, Zhixin Shan, Chunyu Deng, Zili Liao, Hai Deng, Hongtao Liao, Yumei Xue, Wanqun Chen, Xianzhang Zhan, Bin Zhang, Shulin Wu
BACKGROUND: This study was designed to identify the pathogenic mutation in a Chinese family with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) using whole genome sequencing (WGS). METHODS AND RESULTS: Probands II:1 and II:2 underwent routine examinations for diagnosis. Genomic DNA was extracted from the peripheral blood of family members and analyzed using WGS. A total of 60,285 single-nucleotide polymorphisms (SNP) and 13,918 insertions/deletions (InDel) occurring in the exonic regions of genes and predisposing to cardiomyopathies and arrhythmias were identified...
2017: Cardiology
https://www.readbyqxmd.com/read/28504961/wnt-%C3%AE-catenin-pathway-in-arrhythmogenic-cardiomyopathy
#20
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...
April 27, 2017: Oncotarget
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