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https://www.readbyqxmd.com/read/27909533/patient-specific-induced-pluripotent-stem-cell-derived-cardiomyocytes-for-drug-development-and-screening-in-catecholaminergic-polymorphic-ventricular-tachycardia
#1
REVIEW
Ben Jehuda Ronen, Barad Lili
Catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia often leading to sudden cardiac death in children and young adults, is characterized by polymorphic/bidirectional ventricular tachycardia induced by adrenergic stimulation associated with emotionally stress or physical exercise. There are two forms of CPVT: 1. CPVT1 is caused by mutations in the RYR2 gene, encoding for ryanodine receptor type 2. CPVT1 is the most common form of CPVT in the population, and is inherited by a dominant mechanism...
August 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/27882143/expression-of-connexin-43-ion-channels-and-ca-2-handling-proteins-in-rat-pulmonary-vein-cardiomyocytes
#2
Yaqiong Xiao, Xue Cai, Andrew Atkinson, Sunil Jit Logantha, Mark Boyett, Halina Dobrzynski
Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF is thought to be triggered by ectopic beats, originating primarily in the myocardial sleeves surrounding the pulmonary veins (PVs). The mechanisms underlying these cardiac arrhythmias remain unclear. To investigate this, frozen sections of heart and lung tissue from adult rats without arrhythmia were obtained in different planes, stained with Masson's trichrome, and immunolabeled for connexin 43 (Cx43), caveolin-3 (Cav3), hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), Nav1...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27866413/disbalance-of-calcium-regulation-related-genes-in-heart-of-broilers-induced-by-selenium-deficiency
#3
Ziwei Zhang, Man Liu, Zhenqiong Guan, Jie Yang, Zhonghua Liu, Shiwen Xu
Dietary selenium (Se) deficiency may influence the calcium (Ca) homeostasis in broilers. Our objective was to investigate the effects of Se deficiency on Ca regulation related genes' change in heart of broilers. In the present study, 1-day-old broilers were fed either a commercial diet (as control group) with 0.15 mg/kg Se or a Se-deficient diet (as L group) with 0.033 mg/kg Se for 35 days. We examined the mRNA expression levels of 15 Ca regulation related genes (ITPR 1, ITPR 2, ITPR3, RyR2, RyR3, SERCA1s, SLC8A1, PMCA1, CACNA1S, TRPC1, TRPC3, STIM1, ORAI1, CaLM and CRT) in the heart of broilers...
November 21, 2016: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/27866274/ryanodine-receptor-type-3-does-not-contribute-to-contractions-in-the-mouse-myometrium-regardless-of-pregnancy
#4
Katsuhito Matsuki, Masashi Takemoto, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Hiroshi Takeshima, Yuji Imaizumi
Ryanodine receptor type 3 (RyR3) is expressed in myometrial smooth muscle cells (MSMCs). The short isoform of RyR3 is a dominant negative variant (DN-RyR3) and negatively regulates the functions of RyR2 and full-length (FL)-RyR3. DN-RyR3 has been suggested to function as a major RyR3 isoform in non-pregnant (NP) mouse MSMCs, and FL-RyR3 may also be upregulated during pregnancy (P). This increase in the FL-RyR3/DN-RyR3 ratio may contribute to the strong contractions by MSMCs for parturition. In the present study, spontaneous contractions by the myometrium in NP and P mice were highly susceptible to nifedipine but were not affected by ryanodine...
November 20, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27861184/catecholaminergic-polymorphic-ventricular-tachycardia-a-model-for-genotype-specific-therapy
#5
Thomas M Roston, Filip Van Petegem, Shubhayan Sanatani
PURPOSE OF REVIEW: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a life-threatening syndrome defined by exercise-induced or emotion-induced ventricular arrhythmias, typically caused by gain-of-function mutations in RYR2-encoded ryanodine receptor-2 (RyR2). This review will discuss recent advances and ongoing challenges in devising genotype-specific CPVT therapies. RECENT FINDINGS: CPVT patients were once universally thought to be at high risk of sudden death; however, as more cases emerge, CPVT is being re-defined as a complex syndrome of variable expressivity...
January 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/27857207/genomic-contributors-to-atrial-electroanatomical-remodeling-and-atrial-fibrillation-progression-pathway-enrichment-analysis-of-gwas-data
#6
Daniela Husser, Laura Ueberham, Borislav Dinov, Jedrzej Kosiuk, Jelena Kornej, Gerhard Hindricks, M Benjamin Shoemaker, Dan M Roden, Andreas Bollmann, Petra Büttner
In atrial fibrillation (AF), left atrial diameter (LAD) and low voltage area (LVA) are intermediate phenotypes that are associated with AF type and progression. In this study, we tested the hypothesis, that these phenotypes share common, genetically-determined pathways using pathway enrichment analysis of GWAS data. Samples from 660 patients with paroxysmal (n = 370) or persistent AF (n = 290) were genotyped for ~1,000,000 SNPs. SNPs found significantly associated with LAD, LVA or AF type were used for gene-based association tests in a systematic biological Knowledge-based mining system for Genome-wide Genetic studies (KGG)...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27818320/suppression-of-function-mutations-in-the-cardiac-ryanodine-receptor-emerging-evidence-for-a-novel-arrhythmia-syndrome
#7
EDITORIAL
Thomas M Roston, Shubhayan Sanatani, S R Wayne Chen
No abstract text is available yet for this article.
November 3, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27789712/the-cytoplasmic-region-of-inner-helix-s6-is-an-important-determinant-of-cardiac-ryanodine-receptor-channel-gating
#8
Bo Sun, Wenting Guo, Xixi Tian, Jinjing Yao, Lin Zhang, Ruiwu Wang, S R Wayne Chen
The ryanodine receptor (RyR) channel pore is formed by four S6 inner helices with its intracellular gate located at the S6 helix bundle crossing region. The cytoplasmic region of the extended S6 helix is held by the U-motif of the Central domain, and is thought to control the opening and closing of the S6 helix bundle. However, the functional significance of the S6 cytoplasmic region in channel gating is unknown. Here we assessed the role of the S6 cytoplasmic region in the function of cardiac RyR (RyR2) via structure-guided site-directed mutagenesis...
October 27, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27771715/er-stress-via-chop-pathway-is-involved-in-fk506-induced-apoptosis-in-rat-fibroblasts
#9
Jian Tang, Yingbin Ge, Lei Yang, Xinyu Xu, Tao Sui, Dawei Ge, Jun Que, Xiaojian Cao
BACKGROUND/AIMS: Hypertrophic scars (HS) formation results from reduced apoptosis and increased proliferation of fibroblasts. Therefore, apoptosis of fibroblasts is a key target for the development of novel therapeutic strategies for HS. Previous reports demonstrated that FK506 could attenuate scar formation in vivo and FK506 could also induce endoplasmic reticulum stress (ER stress). However, the effects of FK506 on ER stress-mediated apoptosis in fibroblasts remain unclear. METHODS: Rat skin fibroblasts were used in the study...
October 24, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27771553/correction-of-impaired-calmodulin-binding-to-ryr2-as-a-novel-therapy-for-lethal-arrhythmia-in-the-pressure-overloaded-heart-failure
#10
Takayoshi Kato, Takeshi Yamamoto, Yoshihide Nakamura, Takuma Nanno, Go Fukui, Yoko Sufu, Yoriomi Hamada, Takako Maeda, Shigehiko Nishimura, Hironori Ishiguchi, Wakako Murakami, Masakazu Fukuda, Xiaojuan Xu, Akihiro Hino, Makoto Ono, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Noritaka Koseki, Hiroyuki Kyushiki, Masafumi Yano
BACKGROUND: Calmodulin (CaM) is a key modulator of the channel gating function of the ryanodine receptor (RyR). OBJECTIVE: The purpose of this study was to investigate the pathogenic role of RyR-bound CaM in diastolic Ca(2+) leakage from the sarcoplasmic reticulum and arrhythmogenesis in pressure-overloaded heart failure. METHODS: Pressure overload was induced in 12-week-old mice by transverse aortic constriction (TAC) using a 27-gauge needle...
October 19, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27761157/current-topics-in-catecholaminergic-polymorphic-ventricular-tachycardia
#11
Naokata Sumitomo
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is induced by emotions or exercise in patients without organic heart disease and may be polymorphic or bidirectional in nature. The prognosis of CPVT is not good, and therefore prevention of sudden death is of utmost importance. Genetic variants of CPVT include RyR2, CASQ2, CALM2, TRD, and possibly KCNJ2 and ANK2 gene mutations. Hypotheses that suggest the causes of CPVT include weakened binding of FKBP12.6 and RyR2, a store overload-induced Ca(2+) release (SOICR), unzipping of intramolecular domain interactions in RyR2, and molecular and functional abnormalities caused by mutations in the CASQ2 gene...
October 2016: Journal of Arrhythmia
https://www.readbyqxmd.com/read/27760414/junctophilin-2-gene-therapy-rescues-heart-failure-by-normalizing-ryr2-mediated-ca-2-release
#12
Julia O Reynolds, Ann P Quick, Qiongling Wang, David L Beavers, Leonne E Philippen, Jordan Showell, Giselle Barreto-Torres, Donna J Thuerauf, Shirin Doroudgar, Christopher C Glembotski, Xander H T Wehrens
BACKGROUND: Junctophilin-2 (JPH2) is the primary structural protein for the coupling of transverse (T)-tubule associated cardiac L-type Ca channels and type-2 ryanodine receptors on the sarcoplasmic reticulum within junctional membrane complexes (JMCs) in cardiomyocytes. Effective signaling between these channels ensures adequate Ca-induced Ca release required for normal cardiac contractility. Disruption of JMC subcellular domains, a common feature of failing hearts, has been attributed to JPH2 downregulation...
December 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27756708/a-type-2-ryanodine-receptor-variant-associated-with-reduced-ca-2-release-and-short-coupled-torsade-de-pointe-ventricular-arrhythmia
#13
Yusuke Fujii, Hideki Itoh, Seiko Ohno, Takashi Murayama, Nagomi Kurebayashi, Hisaaki Aoki, Malorie Blancard, Yoshihisa Nakagawa, Satoshi Yamamoto, Yumie Matsui, Mari Ichikawa, Keiko Sonoda, Tomoya Ozawa, Kimie Ohkubo, Ichiro Watanabe, Pascale Guicheney, Minoru Horie
BACKGROUND: Ventricular fibrillation (VF) may be caused by premature ventricular contractions (PVCs) whose coupling intervals are under 300ms, a characteristic of scTdP. OBJECTIVE: The purpose of this study is to analyze the underlying RyR2 variants in patients with the short-coupled variant of torsade de pointes (scTdP). METHODS: Seven patients with scTdP (34±12 years old, 3 females) were enrolled in this study. The RyR2 gene was screened by targeted gene sequencing methods, and variant minor allele frequency (MAF) was confirmed in three databases, and the pathogenicity was investigated in multiple in silico tools...
October 15, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27753939/os-06-04-changes-in-gene-expression-pathways-predict-delayed-sodium-excretion-during-saline-infusion
#14
Steven Hunt, Paul Hopkins, Nazeem Nanjee, Karen Schwander, Donald Kohan, D C Rao, Gordon Williams
OBJECTIVE: Identify the earliest hormonal, electrolyte and gene expression responses to a saline infusion before compensatory mechanisms are activated and relate these responses to delayed sodium excretion. DESIGN AND METHOD: 233 normotensive subjects with a strong positive family history of hypertension, ages 21-65, were studied on a low sodium diet before, during and after a 2-hour, 2-liter saline infusion. Plasma and urine hormones of the renin-angiotensin-aldosterone, catecholamine, uric acid, kallikrein, and cortisol pathways, microalbumin, and urine and plasma electrolytes were measured...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27747307/neuronal-na-channels-are-integral-components-of-pro-arrhythmic-na-ca-2-signaling-nanodomain-that-promotes-cardiac-arrhythmias-during-%C3%AE-adrenergic-stimulation
#15
Przemysław B Radwański, Hsiang-Ting Ho, Rengasayee Veeraraghavan, Lucia Brunello, Bin Liu, Andriy E Belevych, Sathya D Unudurthi, Michael A Makara, Silvia G Priori, Pompeo Volpe, Antonis A Armoundas, Wolfgang H Dillmann, Bjorn C Knollmann, Peter J Mohler, Thomas J Hund, Sándor Györke
BACKGROUND: Cardiac arrhythmias are a leading cause of death in the US. Vast majority of these arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT) are associated with increased levels of circulating catecholamines and involve abnormal impulse formation secondary to aberrant Ca(2+) and Na(+) handling. However, the mechanistic link between β-AR stimulation and the subcellular/molecular arrhythmogenic trigger(s) remains elusive. METHODS AND RESULTS: We performed functional and structural studies to assess Ca(2+) and Na(+) signaling in ventricular myocyte as well as surface electrocardiograms in mouse models of cardiac calsequestrin (CASQ2)-associated CPVT...
June 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/27747100/altered-left-ventricular-ion-channel-transcriptome-in-a-high-fat-fed-rat-model-of-obesity-insight-into-obesity-induced-arrhythmogenesis
#16
Reza Ashrafi, Marianne Yon, Lucy Pickavance, Joseph Yanni Gerges, Gershan Davis, John Wilding, Kun Jian, Henggui Zhang, George Hart, Mark Boyett
Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR...
2016: Journal of Obesity
https://www.readbyqxmd.com/read/27737958/mechanical-stress-conditioning-and-electrical-stimulation-promote-contractility-and-force-maturation-of-induced-pluripotent-stem-cell-derived-human-cardiac-tissue
#17
Jia-Ling Ruan, Nathaniel L Tulloch, Maria V Razumova, Mark Saiget, Veronica Muskheli, Lil Pabon, Hans Reinecke, Michael Regnier, Charles E Murry
BACKGROUND: Tissue engineering enables the generation of functional human cardiac tissue with cells derived in vitro in combination with biocompatible materials. Human-induced pluripotent stem cell-derived cardiomyocytes provide a cell source for cardiac tissue engineering; however, their immaturity limits their potential applications. Here we sought to study the effect of mechanical conditioning and electric pacing on the maturation of human-induced pluripotent stem cell-derived cardiac tissues...
November 15, 2016: Circulation
https://www.readbyqxmd.com/read/27737323/thyroxine-increases-serca2-and-ryr2-gene-expression-in-heart-failure-rats-with-euthyroid-sick-syndrome
#18
Fábio V G Campanha, Denise Perone, Dijon H S de Campos, Renata de A M Luvizotto, Maria T De Síbio, Miriane de Oliveira, Regiane M C Olimpio, Fernanda C F Moretto, Carlos R Padovani, Gláucia M F S Mazeto, Antonio C Cicogna, Célia R Nogueira
Objective: The current study was aimed at analyzing sarcoplasmic reticulum Ca2+ ATPase (Serca2) and ryanodine receptor type 2 (Ryr2) gene expression in rats subjected to surgery that induced HF and were subsequently treated with T4 using physiological doses. Materials and methods: HF was induced in 18 male Wistar rats by clipping the ascending thoracic aorta to generate aortic stenosis (HFS group), while the control group (9-sham) underwent thoracotomy. After 21 weeks, the HFS group was subdivided into two subgroups...
October 10, 2016: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27733687/enhanced-cytosolic-ca2-activation-underlies-a-common-defect-of-central-domain-cardiac-ryanodine-receptor-mutations-linked-to-arrhythmias
#19
Zhichao Xiao, Wenting Guo, Bo Sun, Donald J Hunt, Jinhong Wei, Yingjie Liu, Yundi Wang, Ruiwu Wang, Peter P Jones, Thomas G Back, S R Wayne Chen
Recent three-dimensional structural studies reveal that the central domain of ryanodine receptor (RyR) serves as a transducer that converts long-range conformational changes into the gating of the channel pore. Interestingly, the central domain encompasses one of the mutation hotspots (corresponding to amino acid residues 3778-4201) that contains a number of cardiac RyR (RyR2) mutations associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) and atrial fibrillation (AF). However, the functional consequences of these central domain RyR2 mutations are not well understood...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27729468/striated-muscle-preferentially-expressed-protein-kinase-speg-is-essential-for-cardiac-function-by-regulating-junctional-membrane-complex-activity
#20
Ann P Quick, Qiongling Wang, Leonne E Philippen, Giselle Barreto-Torres, David Y Chiang, David L Beavers, Guoliang Wang, Maha Khalid, Julia O Reynolds, Hannah M Campbell, Jordan Showell, Mark D McCauley, Arjen Scholten, Xander H Wehrens
RATIONALE: Junctional membrane complexes (JMC) in myocytes are critical microdomains, in which excitation-contraction coupling occurs. Structural and functional disruption of JMCs underlies contractile dysfunction in failing hearts. However, the role of newly identified JMC protein striated muscle preferentially expressed gene (SPEG) remains unclear. OBJECTIVE: To determine the role of SPEG in healthy and failing adult hearts. MMethods and Results: Proteomic analysis of immunoprecipatated JMC-proteins ryanodine receptor type-2 (RyR2) and junctophilin-2 (JPH2) followed by mass spectrometry identified the serine-threonine kinase SPEG as the only novel binding partner for both proteins...
October 11, 2016: Circulation Research
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