scholarly journals New Insights into the Development and Morphogenesis of the Cardiac Purkinje Fiber Network: Linking Architecture and Function

2021 ◽  
Vol 8 (8) ◽  
pp. 95
Author(s):  
Caroline Choquet ◽  
Lucie Boulgakoff ◽  
Robert G. Kelly ◽  
Lucile Miquerol
Keyword(s):  
Cardiac Conduction ◽  
Purkinje Fiber ◽  
Primary Ring ◽  
Fiber Network ◽  
Conduction Disturbances ◽  
Function Relationship ◽  
And Function ◽  
Cardiac Transcription Factors ◽  
Ventricular Conduction ◽  
Ventricular Trabeculae

The rapid propagation of electrical activity through the ventricular conduction system (VCS) controls spatiotemporal contraction of the ventricles. Cardiac conduction defects or arrhythmias in humans are often associated with mutations in key cardiac transcription factors that have been shown to play important roles in VCS morphogenesis in mice. Understanding of the mechanisms of VCS development is thus crucial to decipher the etiology of conduction disturbances in adults. During embryogenesis, the VCS, consisting of the His bundle, bundle branches, and the distal Purkinje network, originates from two independent progenitor populations in the primary ring and the ventricular trabeculae. Differentiation into fast-conducting cardiomyocytes occurs progressively as ventricles develop to form a unique electrical pathway at late fetal stages. The objectives of this review are to highlight the structure–function relationship between VCS morphogenesis and conduction defects and to discuss recent data on the origin and development of the VCS with a focus on the distal Purkinje fiber network.

scholarly journals Nkx2-5 defines distinct scaffold and recruitment phases during formation of the murine cardiac Purkinje fiber network

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Caroline Choquet ◽  
Robert G. Kelly ◽  
Lucile Miquerol
Keyword(s):  
Transcription Factor ◽  
Electrical Activity ◽  
Cell Fate ◽  
Clonal Analysis ◽  
Conduction System ◽  
Purkinje Fiber ◽  
Fate Mapping ◽  
Fiber Network ◽  
Apply Genetic ◽  
Ventricular Conduction

Abstract The ventricular conduction system coordinates heartbeats by rapid propagation of electrical activity through the Purkinje fiber (PF) network. PFs share common progenitors with contractile cardiomyocytes, yet the mechanisms of segregation and network morphogenesis are poorly understood. Here, we apply genetic fate mapping and temporal clonal analysis to identify murine cardiomyocytes committed to the PF lineage as early as E7.5. We find that a polyclonal PF network emerges by progressive recruitment of conductive precursors to this scaffold from a pool of bipotent progenitors. At late fetal stages, the segregation of conductive cells increases during a phase of rapid recruitment to build the definitive PF network through a non-cell autonomous mechanism. We also show that PF differentiation is impaired in Nkx2-5 haploinsufficient embryos leading to failure to extend the scaffold. In particular, late fetal recruitment fails, resulting in PF hypoplasia and persistence of bipotent progenitors. Our results identify how transcription factor dosage regulates cell fate divergence during distinct phases of PF network morphogenesis.

Electrocardiographic Findings in Psoriatic Arthritis: A Case-Controlled Study

2008 ◽  
Vol 35 (12) ◽  
pp. 2379-2382 ◽  
Author(s):  
JOY FELD ◽  
GIORA WEISS ◽  
ITZHAK ROSNER ◽  
MICHAEL ROZENBAUM ◽  
ARIE LAOR ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Atrioventricular Node ◽  
Cardiac Conduction ◽  
Controlled Study ◽  
Antiinflammatory Drugs ◽  
Conduction Disturbances ◽  
Pr Interval ◽  
Electrocardiographic Findings ◽  
Electrocardiogram Ecg ◽  
Ventricular Conduction

ObjectiveWe assessed cardiac conduction properties in patients with psoriatic arthritis (PsA).MethodsElectrocardiogram (ECG) scans of 92 patients with PsA were compared to 92 age and sex matched nonpsoriatic, nonarthritic patients from general practice serving as controls.ResultsPR interval was found to be significantly longer in the PsA group compared to controls, 159.6 ± 21 ms versus 151.3 ± 26 ms, respectively (p = 0.021). No statistical difference was found with respect to the QRS interval or other atrial or ventricular conduction disturbances studied. No correlation was found between the PR interval and disease duration or PsA subtype. The use of non-steroidal antiinflammatory drugs did not affect the PR interval. Methotrexate was not found to influence the PR interval, compared to other disease modifying antirheumatic drugs. Two PsA patients (2.1%) had a PR interval > 0.2 ms. Their prolonged PR interval could not be explained by medication use. The abnormal prolongation of the PR interval was asymptomatic, requiring no additional intervention. No patient had complete heart block.ConclusionOur study may suggest subtle involvement of the atrioventricular node in patients with PsA.

scholarly journals Nkx2-5 defines distinct scaffold and recruitment phases during formation of the cardiac Purkinje fiber network

2020 ◽  
Author(s):  
Caroline Choquet ◽  
Robert G. Kelly ◽  
Lucile Miquerol
Keyword(s):  
Transcription Factor ◽  
Electrical Activity ◽  
Cell Fate ◽  
Clonal Analysis ◽  
Conduction System ◽  
Purkinje Fiber ◽  
Fate Mapping ◽  
Fiber Network ◽  
Apply Genetic ◽  
Ventricular Conduction

AbstractThe ventricular conduction system coordinates heartbeats by rapid propagation of electrical activity through the Purkinje fiber (PF) network. PFs share common progenitors with contractile cardiomyocytes, yet the mechanisms of segregation and network morphogenesis are poorly understood. In this study, we apply genetic fate mapping and temporal clonal analysis to identify cardiomyocytes committed to the PF lineage as early as E7.5. We find that a polyclonal PF network emerges by progressive recruitment of conductive precursors to this scaffold from a pool of bipotent progenitors. At late fetal stages, the segregation of conductive cells increases during a phase of rapid recruitment to build the definitive PF network through a non-cell autonomous mechanism. We also show that PF differentiation is impaired in Nkx2-5 haploinsufficient embryos leading to failure to extend the scaffold. In particular, late fetal recruitment fails, resulting in PF hypoplasia and persistence of bipotent progenitors. Our results identify how transcription factor dosage regulates cell fate divergence during distinct phases of PF network morphogenesis.

scholarly journals The Evolving Roles of Cardiac Macrophages in Homeostasis, Regeneration, and Repair

2021 ◽  
Vol 22 (15) ◽  
pp. 7923
Author(s):  
Santiago Alvarez-Argote ◽  
Caitlin C. O’Meara
Keyword(s):  
Cardiac Injury ◽  
Cardiac Regeneration ◽  
Normal Function ◽  
Cardiac Conduction ◽  
Cell Detection ◽  
Fate Mapping ◽  
The Novel ◽  
Functional Roles ◽  
Macrophage Populations ◽  
And Function

Macrophages were first described as phagocytic immune cells responsible for maintaining tissue homeostasis by the removal of pathogens that disturb normal function. Historically, macrophages have been viewed as terminally differentiated monocyte-derived cells that originated through hematopoiesis and infiltrated multiple tissues in the presence of inflammation or during turnover in normal homeostasis. However, improved cell detection and fate-mapping strategies have elucidated the various lineages of tissue-resident macrophages, which can derive from embryonic origins independent of hematopoiesis and monocyte infiltration. The role of resident macrophages in organs such as the skin, liver, and the lungs have been well characterized, revealing functions well beyond a pure phagocytic and immunological role. In the heart, recent research has begun to decipher the functional roles of various tissue-resident macrophage populations through fate mapping and genetic depletion studies. Several of these studies have elucidated the novel and unexpected roles of cardiac-resident macrophages in homeostasis, including maintaining mitochondrial function, facilitating cardiac conduction, coronary development, and lymphangiogenesis, among others. Additionally, following cardiac injury, cardiac-resident macrophages adopt diverse functions such as the clearance of necrotic and apoptotic cells and debris, a reduction in the inflammatory monocyte infiltration, promotion of angiogenesis, amelioration of inflammation, and hypertrophy in the remaining myocardium, overall limiting damage extension. The present review discusses the origin, development, characterization, and function of cardiac macrophages in homeostasis, cardiac regeneration, and after cardiac injury or stress.

scholarly journals Network-based approaches to quantify multicellular development

2017 ◽  
Vol 14 (135) ◽  
pp. 20170484 ◽  
Author(s):  
Matthew D. B. Jackson ◽  
Salva Duran-Nebreda ◽  
George W. Bassel
Keyword(s):  
Structure Function ◽  
Spatial Relations ◽  
Higher Order ◽  
Cellular Interaction ◽  
Cellular Organization ◽  
Multicellular Development ◽  
Cell Organization ◽  
Function Relationship ◽  
And Function ◽  
The Relationship

Multicellularity and cellular cooperation confer novel functions on organs following a structure–function relationship. How regulated cell migration, division and differentiation events generate cellular arrangements has been investigated, providing insight into the regulation of genetically encoded patterning processes. Much less is known about the higher-order properties of cellular organization within organs, and how their functional coordination through global spatial relations shape and constrain organ function. Key questions to be addressed include: why are cells organized in the way they are? What is the significance of the patterns of cellular organization selected for by evolution? What other configurations are possible? These may be addressed through a combination of global cellular interaction mapping and network science to uncover the relationship between organ structure and function. Using this approach, global cellular organization can be discretized and analysed, providing a quantitative framework to explore developmental processes. Each of the local and global properties of integrated multicellular systems can be analysed and compared across different tissues and models in discrete terms. Advances in high-resolution microscopy and image analysis continue to make cellular interaction mapping possible in an increasing variety of biological systems and tissues, broadening the further potential application of this approach. Understanding the higher-order properties of complex cellular assemblies provides the opportunity to explore the evolution and constraints of cell organization, establishing structure–function relationships that can guide future organ design.

scholarly journals Regulation of Cardiac Conduction and Arrhythmias by Ankyrin/Spectrin-Based Macromolecular Complexes

2021 ◽  
Vol 8 (5) ◽  
pp. 48
Author(s):  
Drew Nassal ◽  
Jane Yu ◽  
Dennison Min ◽  
Cemantha Lane ◽  
Rebecca Shaheen ◽  
...  
Keyword(s):  
Ion Channels ◽  
Cardiac Disease ◽  
Conduction System ◽  
Cytoskeletal Proteins ◽  
Cardiac Conduction ◽  
Proper Function ◽  
Cardiac Conduction System ◽  
Loss Of Function ◽  
Macromolecular Complexes ◽  
Conduction Disturbances

The cardiac conduction system is an extended network of excitable tissue tasked with generation and propagation of electrical impulses to signal coordinated contraction of the heart. The fidelity of this system depends on the proper spatio-temporal regulation of ion channels in myocytes throughout the conduction system. Importantly, inherited or acquired defects in a wide class of ion channels has been linked to dysfunction at various stages of the conduction system resulting in life-threatening cardiac arrhythmia. There is growing appreciation of the role that adapter and cytoskeletal proteins play in organizing ion channel macromolecular complexes critical for proper function of the cardiac conduction system. In particular, members of the ankyrin and spectrin families have emerged as important nodes for normal expression and regulation of ion channels in myocytes throughout the conduction system. Human variants impacting ankyrin/spectrin function give rise to a broad constellation of cardiac arrhythmias. Furthermore, chronic neurohumoral and biomechanical stress promotes ankyrin/spectrin loss of function that likely contributes to conduction disturbances in the setting of acquired cardiac disease. Collectively, this review seeks to bring attention to the significance of these cytoskeletal players and emphasize the potential therapeutic role they represent in a myriad of cardiac disease states.

scholarly journals Prevalence and Prognostic Relevance of Ventricular Conduction Disturbances in Patients With Aortic Stenosis

2017 ◽  
Vol 120 (12) ◽  
pp. 2226-2232 ◽  
Author(s):  
Edgard A. Prihadi ◽  
Melissa Leung ◽  
E. Mara Vollema ◽  
Arnold C.T. Ng ◽  
Nina Ajmone Marsan ◽  
...  
Keyword(s):  
Aortic Stenosis ◽  
Conduction Disturbances ◽  
Prognostic Relevance ◽  
Ventricular Conduction
Sign in / Sign up

Export Citation Format

Share Document