scholarly journals Screening for circulating miR-208a and -b in different cardiac arrhythmias of dogs

2018 ◽  
Vol 62 (3) ◽  
pp. 359-363 ◽  
Author(s):  
Agnieszka Noszczyk-Nowak ◽  
Maciej Zacharski ◽  
Marcin Michałek
Keyword(s):  
Cardiac Arrhythmias ◽  
High Sensitivity ◽  
Tissue Expression ◽  
Heart Tissue ◽  
Treatment Monitoring ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Canine Heart ◽  
Serum Samples ◽  
Novel Mirna

AbstractIntroductionIn recent years, the high sensitivity and specificity of novel miRNA biomarkers have been utilised for early diagnosis and treatment monitoring of various diseases. Previous reports showed that abnormal expression of miR-208 in mice resulted in the development of an aberrant cardiac conduction system and consecutive arrhythmias. On the other hand, a study on infarcted human heart tissue showed upregulation of miR-208a in subjects with ventricular tachyarrhythmias compared to healthy controls. We prospectively investigated the expression of miR-208a and -208b in the serum of dogs presenting different cardiac arrhythmias.Material and MethodsA total of 28 dogs with atrial fibrillation (n = 8), ventricular premature contractions (n=6), conduction system disturbances (n = 7), and free of heart conditions (as controls) (n = 7) were enrolled in the study. Total RNA was extracted from serum samples and miR-208a and -b, miR-16 as well as a cel-miR-39-5p spike-in were analysed with qPCR and ddPCR.ResultsmiR-208a and miR-208b were not expressed in any of the samples. The calculated ddPCR miR-16 relative expression (normalised with cel-miR-39 spike-in) showed a good correlation (r = 0.82; P < 0.001) with the qPCR results.ConclusionThis outcome warrants further investigation, possibly focusing on tissue expression of miR-208 in the canine heart.

Abstract MP239: Hippo Signaling Pathway Maintains Homeostasis Of The Cardiac Conduction System

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Mingjie Zheng ◽  
Jun Wang
Keyword(s):  
Signaling Pathway ◽  
Calcium Homeostasis ◽  
Cardiac Arrhythmias ◽  
Critical Role ◽  
Conduction System ◽  
Conditional Knockout ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

The cardiac conduction system (CCS) is required for initiating and maintaining regular rhythmic heartbeats. The fundamental Hippo signaling pathway plays critical roles in the heart, yet its role in the CCS remains largely unknown. Here, we found that conditional knockout (CKO) of Hippo signaling kinases Lats1 and Lats2 in the CCS using Hcn4 CreERT2 , led to cardiac arrhythmias in adult mice. Compared with controls, Lats1/2 CKO mutant mice had disrupted calcium homeostasis, increased fibrosis and more fibroblast proliferation in the sinoatrial node. Deletion of the Hippo signaling effectors Yap and Taz in the CCS rescued phenotypes caused by Lats1/2 deletion, and these mice had rescued sinus rhythm and reduced fibrosis, which indicated that Lats1/2 function through Yap and Taz in CCS. Our Cleavage Under Targets and Tagmentation (CUT&Tag)-sequencing using Yap antibody followed by RNA-Seq revealed that Yap directly regulates calcium homeostasis genes such as Ryr2 and fibrosis induction genes such as TGF-β family. Further, we discovered that miR-17-92 represses Hippo signaling by directly suppressing Lats2 expression. miR-17-92 CKO in the CCS led to increased Hippo signaling activity and cardiac arrhythmias, indicating that a fine-tuned level of Hippo signaling is critical for CCS homeostasis. Together, our findings reveal the critical role of a miR-Hippo-Yap genetic pathway in maintaining CCS homeostasis.

scholarly journals The Link Between Sex Hormones and Susceptibility to Cardiac Arrhythmias: From Molecular Basis to Clinical Implications

2021 ◽  
Vol 8 ◽  
Author(s):  
Sarah Costa ◽  
Ardan M. Saguner ◽  
Alessio Gasperetti ◽  
Deniz Akdis ◽  
Corinna Brunckhorst ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Cardiac Arrhythmias ◽  
Molecular Basis ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Clinical Implications ◽  
Cardiac Ion Channels ◽  
Increased Risk ◽  
Qt Syndrome ◽  
Underlying Mechanisms

It is well-known that gender is an independent risk factor for some types of cardiac arrhythmias. For example, males have a greater prevalence of atrial fibrillation and the Brugada Syndrome. In contrast, females are at increased risk for the Long QT Syndrome. However, the underlying mechanisms of these gender differences have not been fully identified. Recently, there has been accumulating evidence indicating that sex hormones may have a significant impact on the cardiac rhythm. In this review, we describe in-depth the molecular interactions between sex hormones and the cardiac ion channels, as well as the clinical implications of these interactions on the cardiac conduction system, in order to understand the link between these hormones and the susceptibility to arrhythmias.

Abstract 531: Mechanistic and Functional Differences in Rna Binding and Processing Activities of the Muscle- and Non-muscle Rbfox2 Isoforms

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Chaitali Misra ◽  
Ullas Valiya Chembazhi ◽  
Sarah Matatov ◽  
Sushant Bangru ◽  
Auinash Kalsotra
Keyword(s):  
Regulatory Networks ◽  
Rna Binding ◽  
Trinucleotide Repeat ◽  
Splice Variants ◽  
Heart Tissue ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Conduction Delay ◽  
Aberrant Expression ◽  
Splicing Regulators

Myotonic Dystrophy type 1 (DM1), the most prevalent form of adult onset muscular dystrophy, is caused by CTG trinucleotide repeat expansion in the 3’-UTR of DMPK gene. Over 80% of DM1 patients exhibit heart dysfunctions, which are the second leading cause for DM1-related deaths. Recently, we demonstrated that aberrant expression of a non-muscle splice isoform of RNA-binding protein RBFOX2 triggers cardiac conduction delay, atrioventricular heart blocks, and spontaneous arrhythmogenesis in DM1 heart. RBFOX2 is a master regulator of tissue-specific alternative splicing and a pair of mutually exclusive 43-nucleotide(nt) and 40-nt exons in its C-terminal domain encode the muscle (RBFOX2 43 ) and non-muscle (RBFOX2 40 ) isoforms. The RBFOX2 40 isoform is predominantly expressed in the fetal heart, and is replaced by the RBFOX2 43 isoform in development, specifically within the cardiomyocytes of adult hearts. To deconstruct the splicing regulatory networks of RBFOX2 43 and RBFOX2 40 isoforms, characterize their respective RNA binding landscapes, and determine the RBFOX2 40 -driven transcriptome alterations in DM1 heart tissue, we performed eCLIP and high-resolution RNA-sequencing studies on cardiomyocytes isolated from wild type (expressing the normal muscle-specific RBFOX2 43 isoform), Rbfox2 Δ43/Δ43 (expressing the non-muscle RBFOX2 40 isoform), and RBFOX2 40 overexpressing (OE) mice. By integrating genome-wide RNA binding and processing activities for the two RBFOX2 isoforms, we found that a switch from the muscle-specific (RBFOX2 43 ) to non-muscle (RBFOX2 40 ) isoform provokes DM1-like cardiac pathology by altering the mRNA abundance and splicing of genes encoding components of the conduction system and/or contractile apparatus. Further, through subnuclear fractionation and protein-protein interaction studies, we demonstrate that the higher-order assembly of LASR (large assembly of splicing regulators) complexes formed by the RBFOX2 40 isoform boost its splicing activity and promote the generation of pathogenic splice variants of voltage-gated ion channels and other components of the cardiac conduction system.

scholarly journals Progressive cardiac arrhythmias and ECG abnormalities in the Huntington’s disease BACHD mouse model

2019 ◽  
Vol 29 (3) ◽  
pp. 369-381
Author(s):  
Yujie Zhu ◽  
Isaac Shamblin ◽  
Efrain Rodriguez ◽  
Grace E Salzer ◽  
Lita Araysi ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cardiac Arrhythmias ◽  
Structural Changes ◽  
Artificial Chromosome ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Increased Risk ◽  
Ecg Abnormalities

Abstract Huntington’s disease (HD) is a dominantly inherited neurodegenerative disease. There is accumulating evidence that HD patients have increased prevalence of conduction abnormalities and compromised sinoatrial node function which could lead to increased risk for arrhythmia. We used mutant Huntingtin (mHTT) expressing bacterial artificial chromosome Huntington’s disease mice to determine if they exhibit electrocardiogram (ECG) abnormalities involving cardiac conduction that are known to increase risk of sudden arrhythmic death in humans. We obtained surface ECGs and analyzed arrhythmia susceptibility; we observed prolonged QRS duration, increases in PVCs as well as PACs. Abnormal histological and structural changes that could lead to cardiac conduction system dysfunction were seen. Finally, we observed decreases in desmosomal proteins, plakophilin-2 and desmoglein-2, which have been reported to cause cardiac arrhythmias and reduced conduction. Our study indicates that mHTT could cause progressive cardiac conduction system pathology that could increase the susceptibility to arrhythmias and sudden cardiac death in HD patients.

scholarly journals Small RNA-Sequencing: Approaches and Considerations for miRNA Analysis

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 964
Author(s):  
Sarka Benesova ◽  
Mikael Kubista ◽  
Lukas Valihrach
Keyword(s):  
Rna Sequencing ◽  
Small Rna ◽  
High Sensitivity ◽  
Small Rna Sequencing ◽  
Rna Seq ◽  
Liquid Biopsies ◽  
Comprehensive Overview ◽  
Rna Molecules ◽  
Novel Mirna ◽  
The Many

MicroRNAs (miRNAs) are a class of small RNA molecules that have an important regulatory role in multiple physiological and pathological processes. Their disease-specific profiles and presence in biofluids are properties that enable miRNAs to be employed as non-invasive biomarkers. In the past decades, several methods have been developed for miRNA analysis, including small RNA sequencing (RNA-seq). Small RNA-seq enables genome-wide profiling and analysis of known, as well as novel, miRNA variants. Moreover, its high sensitivity allows for profiling of low input samples such as liquid biopsies, which have now found applications in diagnostics and prognostics. Still, due to technical bias and the limited ability to capture the true miRNA representation, its potential remains unfulfilled. The introduction of many new small RNA-seq approaches that tried to minimize this bias, has led to the existence of the many small RNA-seq protocols seen today. Here, we review all current approaches to cDNA library construction used during the small RNA-seq workflow, with particular focus on their implementation in commercially available protocols. We provide an overview of each protocol and discuss their applicability. We also review recent benchmarking studies comparing each protocol’s performance and summarize the major conclusions that can be gathered from their usage. The result documents variable performance of the protocols and highlights their different applications in miRNA research. Taken together, our review provides a comprehensive overview of all the current small RNA-seq approaches, summarizes their strengths and weaknesses, and provides guidelines for their applications in miRNA research.

scholarly journals Sudden Unexpected Death Associated with Arrhythmogenic Cardiomyopathy: Study of the Cardiac Conduction System

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1323
Author(s):  
Giulia Ottaviani ◽  
Graziella Alfonsi ◽  
Simone G. Ramos ◽  
L. Maximilian Buja
Keyword(s):  
Fibromuscular Dysplasia ◽  
Ventricular Myocardium ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Future Research ◽  
Cardiac Conduction System ◽  
Arrhythmogenic Cardiomyopathy ◽  
Unexpected Death ◽  
The Past ◽  
The Right

A retrospective study was conducted on pathologically diagnosed arrhythmogenic cardiomyopathy (ACM) from consecutive cases over the past 34 years (n = 1109). The anatomo-pathological analyses were performed on 23 hearts diagnosed as ACM (2.07%) from a series of 1109 suspected cases, while histopathological data of cardiac conduction system (CCS) were available for 15 out of 23 cases. The CCS was removed in two blocks, containing the following structures: Sino-atrial node (SAN), atrio-ventricular junction (AVJ) including the atrio-ventricular node (AVN), the His bundle (HB), the bifurcation (BIF), the left bundle branch (LBB) and the right bundle branch (RBB). The ACM cases consisted of 20 (86.96%) sudden unexpected cardiac death (SUCD) and 3 (13.04%) native explanted hearts; 16 (69.56%) were males and 7 (30.44%) were females, ranging in age from 5 to 65 (mean age ± SD, 36.13 ± 16.06) years. The following anomalies of the CCS, displayed as percentages of the 15 ACM SUCD cases in which the CCS has been fully analyzed, have been detected: Hypoplasia of SAN (80%) and/or AVJ (86.67%) due to fatty-fibrous involvement, AVJ dispersion and/or septation (46.67%), central fibrous body (CFB) hypoplasia (33.33%), fibromuscular dysplasia of SAN (20%) and/or AVN (26.67%) arteries, hemorrhage and infarct-like lesions of CCS (13.33%), islands of conduction tissue in CFB (13.33%), Mahaim fibers (13.33%), LBB block by fibrosis (13.33%), AVN tongue (13.33%), HB duplicity (6.67%%), CFB cartilaginous meta-hyperplasia (6.67%), and right sided HB (6.67%). Arrhythmias are the hallmark of ACM, not only from the fatty-fibrous disruption of the ventricular myocardium that accounts for reentrant ventricular tachycardia, but also from the fatty-fibrous involvement of CCS itself. Future research should focus on application of these knowledge on CCS anomalies to be added to diagnostic criteria or at least to be useful to detect the patients with higher sudden death risks.

scholarly journals Functional suppression of Kcnq1 leads to early sodium channel remodelling and cardiac conduction system dysmorphogenesis

2013 ◽  
Vol 98 (3) ◽  
pp. 504-514 ◽  
Author(s):  
Angel J. de la Rosa ◽  
Jorge N. Domínguez ◽  
David Sedmera ◽  
Bara Sankova ◽  
Leif Hove-Madsen ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System
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