scholarly journals Gradual differentiation and confinement of the cardiac conduction system as indicated by marker gene expression

2020 ◽  
Vol 1867 (3) ◽  
pp. 118509 ◽  
Author(s):  
Vincent W.W. van Eif ◽  
Sonia Stefanovic ◽  
Rajiv A. Mohan ◽  
Vincent M. Christoffels
Keyword(s):  
Gene Expression ◽  
Marker Gene ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Marker Gene Expression

Abstract MP115: Transcriptional Patterning of the Ventricular Cardiac Conduction System

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Ozanna Burnicka-Turek ◽  
Michael Broman ◽  
Jeffrey D Steimle ◽  
Bastiaan Boukens ◽  
Nataliya B Petrenko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ventricular Arrhythmias ◽  
Regulatory Elements ◽  
Conduction System ◽  
Mouse Genetics ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Gene Expression Network ◽  
T Box

The heart beats 2 billion times over the average human lifespan and is the manifestation of a pattern of cardiomyocyte depolarization organized by a specialized network of cardiomyocytes, the cardiac conduction system (CCS). Patterning of the CCS into atrial node versus ventricular conduction system (VCS) components with distinct physiology is essential for the normal heartbeat and has been recognized for more than a century. However molecular basis of this regional patterning is not well understood. Using mouse genetics, we found that the ratio between T-box transcriptional activator, Tbx5 , and T-box transcriptional repressor, Tbx3 , determines the molecular and functional output of VCS myocytes. Adult VCS-specific removal of Tbx5 or overexpression of Tbx3 re-patterned the fast VCS into slow, nodal-like cells based on molecular, cellular and functional criteria. Specifically, the ventricular fast conduction gene expression network was lost whereas the slow conduction nodal gene expression network was retained. Action potentials (APs) of Tbx5 -deficient VCS myocytes adopted nodal-specific characteristics, including increased AP duration and cellular automaticity. Removal of Tbx5 in-vivo precipitated inappropriate depolarizations in the His-bundle that initiated lethal ventricular arrhythmias. A T-box rheostat mechanism for CCS patterning was confirmed by Tbx5/Tbx3 genetic interaction studies. TBX5 bound and directly activated cis -regulatory elements at fast conduction loci genome-wide, defining the identity of the adult VCS. Furthermore, TBX5 bound and activated cis-regulatory elements at Tbx5 itself, describing a multi-tiered T-box-dependent fast conduction gene regulatory network (GRN). The hierarchical GRN established a bi-stable network in mathematical modeling, with only high or low fast conduction gene expression states, suggesting a genomic mechanism for the establishment of VCS versus nodal states in-vivo . Thus, the CCS is patterned entirely as a slow, nodal ground state, with a T-box dependent, physiologically dominant, fast conduction network driven specifically in the VCS. Disruption of the fast VCS GRN allowed nodal physiology to emerge, providing a molecular mechanism for some lethal ventricular arrhythmias.

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

Sudden death due to lymphomatous infiltration of the cardiac conduction system

2003 ◽  
Vol 12 (2) ◽  
pp. 77-81 ◽  
Author(s):  
Giulia Ottaviani ◽  
Luigi Matturri ◽  
Lino Rossi ◽  
Dan Jones
Keyword(s):  
Sudden Death ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System
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