scholarly journals Role of the Epicardium in the Development of the Atrioventricular Valves and Its Relevance to the Pathogenesis of Myxomatous Valve Disease

2021 ◽  
Vol 8 (5) ◽  
pp. 54
Author(s):  
Renélyn Wolters ◽  
Ray Deepe ◽  
Jenna Drummond ◽  
Andrew B. Harvey ◽  
Emilye Hiriart ◽  
...  
Keyword(s):  
Heart Development ◽  
Molecular Mechanisms ◽  
Valve Disease ◽  
Developmental Defects ◽  
Atrioventricular Valves ◽  
Atrioventricular Junction ◽  
Left Behind ◽  
Cardiovascular Biology ◽  
Valve Formation

This paper is dedicated to the memory of Dr. Adriana “Adri” Gittenberger-de Groot and in appreciation of her work in the field of developmental cardiovascular biology and the legacy that she has left behind. During her impressive career, Dr. Gittenberger-de Groot studied many aspects of heart development, including aspects of cardiac valve formation and disease and the role of the epicardium in the formation of the heart. In this contribution, we review some of the work on the role of epicardially-derived cells (EPDCs) in the development of the atrioventricular valves and their potential involvement in the pathogenesis of myxomatous valve disease (MVD). We provide an overview of critical events in the development of the atrioventricular junction, discuss the role of the epicardium in these events, and illustrate how interfering with molecular mechanisms that are involved in the epicardial-dependent formation of the atrioventricular junction leads to a number of abnormalities. These abnormalities include defects of the AV valves that resemble those observed in humans that suffer from MVD. The studies demonstrate the importance of the epicardium for the proper formation and maturation of the AV valves and show that the possibility of epicardial-associated developmental defects should be taken into consideration when determining the genetic origin and pathogenesis of MVD.

Prenatal ethanol exposure impairs the conduction delay at the atrioventricular junction in the looping heart

2021 ◽  
Author(s):  
Shan Ling ◽  
Michael W Jenkins ◽  
Michiko Watanabe ◽  
Stephanie M Ford ◽  
Andrew M Rollins
Keyword(s):  
Heart Development ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Heart Defects ◽  
Ethanol Exposure ◽  
Cardiac Conduction ◽  
Conduction Delay ◽  
Prenatal Ethanol Exposure ◽  
Endocardial Cushions ◽  
Atrioventricular Junction

The etiology of ethanol-related congenital heart defects has been the focus of much study, but most research has concentrated on cellular and molecular mechanisms. We have shown with optical coherence tomography (OCT) that ethanol exposure led to increased retrograde flow and smaller atrioventricular (AV) cushions compared to controls. Since AV cushions play a role in patterning the conduction delay at the atrioventricular junction (AVJ), this study aims to investigate whether ethanol exposure alters the AVJ conduction in early looping hearts and whether this alteration is related to the decreased cushion size. Quail embryos were exposed to a single dose of ethanol at gastrulation, and Hamburger-Hamilton stage 19 - 20 hearts were dissected for imaging. Cardiac conduction was measured using an optical mapping microscope and we imaged the endocardial cushions using OCT. Our results showed that, compared with controls, ethanol-exposed embryos exhibited abnormally fast AVJ conduction and reduced cushion size. However, this increased conduction velocity (CV) did not strictly correlate with decreased cushion volume and thickness. By matching the CV map to the cushion size map, we found that the slowest conduction location was consistently at the atrial side of the AVJ, which had the thinner cushions, not at the thickest cushion location at the ventricular side as expected. Our findings reveal regional differences in the AVJ myocardium even at this early stage in heart development. These findings reveal the early steps leading to the heterogeneity and complexity of conduction at the mature AVJ, a site where arrhythmias can be initiated.

From cushions to leaflets: morphogenesis of cardiac atrioventricular valves

2018 ◽  
Author(s):  
Donal MacGrogan ◽  
José Maria Pérez-Pomares ◽  
Bill Chaudhry ◽  
José Luis de la Pompa ◽  
Deborah J. Henderson
Keyword(s):  
Heart Development ◽  
Cellular Proliferation ◽  
Valve Disease ◽  
Signalling Pathways ◽  
Valve Leaflet ◽  
Endocardial Cushions ◽  
Developmental Defects ◽  
Mesenchymal Transition ◽  
Valve Development ◽  
Developmental Signalling

At the looping stage of heart development, tissue patterning of myocardium and endocardium at the atrioventricular (AV) junction defines a morphogenic field competent to form valves that initially appear as protrusions of proteoglycan-rich extracellular matrix (ECM) called endocardial cushions (ECs) which are cellularized by an endocardial-mesenchymal transition (EMT). Cellular proliferation results in fusion of the major AV mesenchymal cushions and AV septation, whereas smaller cushions receive a supply from epicardially derived cells. These various sources of mesenchyme precursors give rise to most of the valve structures, leaflets, annuli, and supporting tension apparatus. During valve leaflet maturation, the ECM matrix accumulates collagen and elastin and assembles into a thin flexible fibrous structure, which is remarkably tough. Valve development is regulated by the cross-talk between developmental signalling pathways. Pathogenic mutations in a subset of developmentally important genes have been linked to valve disease, suggesting that developmental defects may underlie valve disease in adulthood.

scholarly journals Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009890
Author(s):  
Anja Bühler ◽  
Bernd M. Gahr ◽  
Deung-Dae Park ◽  
Alberto Bertozzi ◽  
Alena Boos ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Heart Development ◽  
Positional Cloning ◽  
Molecular Mechanisms ◽  
Cardiac Regeneration ◽  
Border Zone ◽  
Cardiomyocyte Proliferation ◽  
Histone Deacetylase 1

In contrast to mammals, the zebrafish maintains its cardiomyocyte proliferation capacity throughout adulthood. However, neither the molecular mechanisms that orchestrate the proliferation of cardiomyocytes during developmental heart growth nor in the context of regeneration in the adult are sufficiently defined yet. We identified in a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen the recessive, embryonic-lethal zebrafish mutant baldrian (bal), which shows severely impaired developmental heart growth due to diminished cardiomyocyte proliferation. By positional cloning, we identified a missense mutation in the zebrafish histone deacetylase 1 (hdac1) gene leading to severe protein instability and the loss of Hdac1 function in vivo. Hdac1 inhibition significantly reduces cardiomyocyte proliferation, indicating a role of Hdac1 during developmental heart growth in zebrafish. To evaluate whether developmental and regenerative Hdac1-associated mechanisms of cardiomyocyte proliferation are conserved, we analyzed regenerative cardiomyocyte proliferation after Hdac1 inhibition at the wound border zone in cryoinjured adult zebrafish hearts and we found that Hdac1 is also essential to orchestrate regenerative cardiomyocyte proliferation in the adult vertebrate heart. In summary, our findings suggest an important and conserved role of Histone deacetylase 1 (Hdac1) in developmental and adult regenerative cardiomyocyte proliferation in the vertebrate heart.

scholarly journals The Role of the Epicardium During Heart Development and Repair

2020 ◽  
Vol 126 (3) ◽  
pp. 377-394 ◽  
Author(s):  
Pearl Quijada ◽  
Michael A. Trembley ◽  
Eric M. Small
Keyword(s):  
Heart Development ◽  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Cardiac Injury ◽  
Single Layer ◽  
Mesenchymal Transition ◽  
Heart Repair ◽  
Heart Formation

The heart is lined by a single layer of mesothelial cells called the epicardium that provides important cellular contributions for embryonic heart formation. The epicardium harbors a population of progenitor cells that undergo epithelial-to-mesenchymal transition displaying characteristic conversion of planar epithelial cells into multipolar and invasive mesenchymal cells before differentiating into nonmyocyte cardiac lineages, such as vascular smooth muscle cells, pericytes, and fibroblasts. The epicardium is also a source of paracrine cues that are essential for fetal cardiac growth, coronary vessel patterning, and regenerative heart repair. Although the epicardium becomes dormant after birth, cardiac injury reactivates developmental gene programs that stimulate epithelial-to-mesenchymal transition; however, it is not clear how the epicardium contributes to disease progression or repair in the adult. In this review, we will summarize the molecular mechanisms that control epicardium-derived progenitor cell migration, and the functional contributions of the epicardium to heart formation and cardiomyopathy. Future perspectives will be presented to highlight emerging therapeutic strategies aimed at harnessing the regenerative potential of the fetal epicardium for cardiac repair.

scholarly journals Role of Signaling Pathways during Cardiomyocyte Differentiation of Mesenchymal Stem Cells

Cardiology ◽  
2021 ◽  
Author(s):  
Leila Soltani ◽  
Amir Hossein Mahdavi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Heart Development ◽  
Molecular Mechanisms ◽  
Adipogenic Differentiation ◽  
Cardiomyocyte Differentiation ◽  
Multipotent Stem Cells ◽  
Promising Source

Multipotent stem cells, including mesenchymal stem cells (MSCs), represent a promising source to be used by regenerative medicine. They are capable of performing myogenic, chondrogenic, osteogenic and adipogenic differentiation. Also, MSCs are characterized by the expression of multiple surface antigens, but none of them appears to be particularly expressed on MSCs. Moreover, the prospect of monitoring and controlling MSC differentiation is a scientifically crucial regulatory and clinical requirement. Different transcription factors and signaling pathways are involved in cardiomyocyte differentiation. Due to the paucity of studies exclusively focused on cardiomyocyte differentiation of MSCs, present study aims at describing the roles of various signaling pathways (FGF, TGF, Wnt, Notch, etc.) in cardiomyocytes differentiation of MSCs. Understanding the signaling pathways that control the commitment and differentiation of cardiomyocyte cells not only will expand our basic understanding of molecular mechanisms of heart development, but also will enable us to develop therapeutic means of intervention in cardiovascular diseases.

scholarly journals The canonical way to make a heart: β-catenin and plakoglobin in heart development and remodeling

2017 ◽  
Vol 242 (18) ◽  
pp. 1735-1745 ◽  
Author(s):  
Oksana O Piven ◽  
Cecilia L Winata
Keyword(s):  
Wnt Signaling ◽  
Heart Development ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Close Relative ◽  
Recent Experimental Data ◽  
Canonical Wnt Signaling ◽  
Functional Features ◽  
Canonical Wnt

The main mediator of the canonical Wnt pathway, β-catenin, is a major effector of embryonic development, postnatal tissue homeostasis, and adult tissue regeneration. The requirement for β-catenin in cardiogenesis and embryogenesis has been well established. However, many questions regarding the molecular mechanisms by which β-catenin and canonical Wnt signaling regulate these developmental processes remain unanswered. An interesting question that emerged from our studies concerns how β-catenin signaling is modulated through interaction with other factors. Recent experimental data implicate new players in canonical Wnt signaling, particularly those which modulate β-catenin function in many its biological processes, including cardiogenesis. One of the interesting candidates is plakoglobin, a little-studied member of the catenin family which shares several mechanistic and functional features with its close relative, β-catenin. Here we have focused on the function of β-catenin in cardiogenesis. We also summarize findings on plakoglobin signaling function and discuss possible interplays between β-catenin and plakoglobin in the regulation of embryonic heart development. Impact statement Heart development, function, and remodeling are complex processes orchestrated by multiple signaling networks. This review examines our current knowledge of the role of canonical Wnt signaling in cardiogenesis and heart remodeling, focusing primarily on the mechanistic action of its effector β-catenin. We summarize the generally accepted understanding of the field based on experimental in vitro and in vivo data, and address unresolved questions in the field, specifically relating to the role of canonical Wnt signaling in heart maturation and regeneration. What are the modulators of canonical Wnt, and particularly what are the potential roles of plakoglobin, a close relative of β-catenin, in regulating Wnt signaling?Answers to these questions will enhance our understanding of the mechanism by which the canonical Wnt signaling regulates development of the heart and its regeneration after damage.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

When People Come First

2013 ◽  
Keyword(s):  
Global Health ◽  
Scale Up ◽  
Moral Economy ◽  
Health Science ◽  
Health It ◽  
Left Behind ◽  
New Research ◽  
Health Enterprise ◽  
Conceptual Work

This book critically assesses the expanding field of global health. It brings together an international and interdisciplinary group of scholars to address the medical, social, political, and economic dimensions of the global health enterprise through vivid case studies and bold conceptual work. The book demonstrates the crucial role of ethnography as an empirical lantern in global health, arguing for a more comprehensive, people-centered approach. Topics include the limits of technological quick fixes in disease control, the moral economy of global health science, the unexpected effects of massive treatment rollouts in resource-poor contexts, and how right-to-health activism coalesces with the increased influence of the pharmaceutical industry on health care. The chapters explore the altered landscapes left behind after programs scale up, break down, or move on. We learn that disease is really never just one thing, technology delivery does not equate with care, and biology and technology interact in ways we cannot always predict. The most effective solutions may well be found in people themselves, who consistently exceed the projections of experts and the medical-scientific, political, and humanitarian frameworks in which they are cast. This book sets a new research agenda in global health and social theory and challenges us to rethink the relationships between care, rights, health, and economic futures.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

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