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J. Cardiovasc. Dev. Dis., Volume 3, Issue 2 (June 2016) – 13 articles

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Review
Vascular Development and Regeneration in the Mammalian Heart
J. Cardiovasc. Dev. Dis. 2016, 3(2), 23; https://doi.org/10.3390/jcdd3020023 - 16 Jun 2016
Cited by 4 | Viewed by 2833
Abstract
Cardiovascular diseases including coronary artery disease are the leading cause of death worldwide. Unraveling the developmental origin of coronary vessels could offer important therapeutic implications for treatment of cardiovascular diseases. The recent identification of the endocardial source of coronary vessels reveals a heterogeneous [...] Read more.
Cardiovascular diseases including coronary artery disease are the leading cause of death worldwide. Unraveling the developmental origin of coronary vessels could offer important therapeutic implications for treatment of cardiovascular diseases. The recent identification of the endocardial source of coronary vessels reveals a heterogeneous origin of coronary arteries in the adult heart. In this review, we will highlight recent advances in finding the sources of coronary vessels in the mammalian heart from lineage-tracing models as well as differentiation studies using pluripotent stem cells. Moreover, we will also discuss how we induce neovascularization in the damaged heart through transient yet highly efficient expression of VEGF-modified mRNAs as a potentially therapeutic delivery platform. Full article
(This article belongs to the Special Issue Myocardial Reprogramming in Development and Regeneration)
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Review
The Popeye Domain Containing Genes and Their Function in Striated Muscle
J. Cardiovasc. Dev. Dis. 2016, 3(2), 22; https://doi.org/10.3390/jcdd3020022 - 15 Jun 2016
Cited by 9 | Viewed by 3056
Abstract
The Popeye domain containing (POPDC) genes encode a novel class of cAMP effector proteins, which are abundantly expressed in heart and skeletal muscle. Here, we will review their role in striated muscle as deduced from work in cell and animal models and the [...] Read more.
The Popeye domain containing (POPDC) genes encode a novel class of cAMP effector proteins, which are abundantly expressed in heart and skeletal muscle. Here, we will review their role in striated muscle as deduced from work in cell and animal models and the recent analysis of patients carrying a missense mutation in POPDC1. Evidence suggests that POPDC proteins control membrane trafficking of interacting proteins. Furthermore, we will discuss the current catalogue of established protein-protein interactions. In recent years, the number of POPDC-interacting proteins has been rising and currently includes ion channels (TREK-1), sarcolemma-associated proteins serving functions in mechanical stability (dystrophin), compartmentalization (caveolin 3), scaffolding (ZO-1), trafficking (NDRG4, VAMP2/3) and repair (dysferlin) or acting as a guanine nucleotide exchange factor for Rho-family GTPases (GEFT). Recent evidence suggests that POPDC proteins might also control the cellular level of the nuclear proto-oncoprotein c-Myc. These data suggest that this family of cAMP-binding proteins probably serves multiple roles in striated muscle. Full article
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Review
A Matter of the Heart: The African Clawed Frog Xenopus as a Model for Studying Vertebrate Cardiogenesis and Congenital Heart Defects
J. Cardiovasc. Dev. Dis. 2016, 3(2), 21; https://doi.org/10.3390/jcdd3020021 - 04 Jun 2016
Cited by 12 | Viewed by 4073
Abstract
The African clawed frog, Xenopus, is a valuable non-mammalian model organism to investigate vertebrate heart development and to explore the underlying molecular mechanisms of human congenital heart defects (CHDs). In this review, we outline the similarities between Xenopus and mammalian cardiogenesis, and provide [...] Read more.
The African clawed frog, Xenopus, is a valuable non-mammalian model organism to investigate vertebrate heart development and to explore the underlying molecular mechanisms of human congenital heart defects (CHDs). In this review, we outline the similarities between Xenopus and mammalian cardiogenesis, and provide an overview of well-studied cardiac genes in Xenopus, which have been associated with congenital heart conditions. Additionally, we highlight advantages of modeling candidate genes derived from genome wide association studies (GWAS) in Xenopus and discuss commonly used techniques. Full article
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
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Review
Genome-Wide Approaches to Drosophila Heart Development
J. Cardiovasc. Dev. Dis. 2016, 3(2), 20; https://doi.org/10.3390/jcdd3020020 - 27 May 2016
Cited by 7 | Viewed by 2911
Abstract
The development of the dorsal vessel in Drosophila is one of the first systems in which key mechanisms regulating cardiogenesis have been defined in great detail at the genetic and molecular level. Due to evolutionary conservation, these findings have also provided major inputs [...] Read more.
The development of the dorsal vessel in Drosophila is one of the first systems in which key mechanisms regulating cardiogenesis have been defined in great detail at the genetic and molecular level. Due to evolutionary conservation, these findings have also provided major inputs into studies of cardiogenesis in vertebrates. Many of the major components that control Drosophila cardiogenesis were discovered based on candidate gene approaches and their functions were defined by employing the outstanding genetic tools and molecular techniques available in this system. More recently, approaches have been taken that aim to interrogate the entire genome in order to identify novel components and describe genomic features that are pertinent to the regulation of heart development. Apart from classical forward genetic screens, the availability of the thoroughly annotated Drosophila genome sequence made new genome-wide approaches possible, which include the generation of massive numbers of RNA interference (RNAi) reagents that were used in forward genetic screens, as well as studies of the transcriptomes and proteomes of the developing heart under normal and experimentally manipulated conditions. Moreover, genome-wide chromatin immunoprecipitation experiments have been performed with the aim to define the full set of genomic binding sites of the major cardiogenic transcription factors, their relevant target genes, and a more complete picture of the regulatory network that drives cardiogenesis. This review will give an overview on these genome-wide approaches to Drosophila heart development and on computational analyses of the obtained information that ultimately aim to provide a description of this process at the systems level. Full article
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
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Article
Cardiac-Restricted Expression of VCP/TER94 RNAi or Disease Alleles Perturbs Drosophila Heart Structure and Impairs Function
J. Cardiovasc. Dev. Dis. 2016, 3(2), 19; https://doi.org/10.3390/jcdd3020019 - 24 May 2016
Cited by 10 | Viewed by 2679
Abstract
Valosin-containing protein (VCP) is a highly conserved mechanoenzyme that helps maintain protein homeostasis in all cells and serves specialized functions in distinct cell types. In skeletal muscle, it is critical for myofibrillogenesis and atrophy. However, little is known about VCP’s role(s) in the [...] Read more.
Valosin-containing protein (VCP) is a highly conserved mechanoenzyme that helps maintain protein homeostasis in all cells and serves specialized functions in distinct cell types. In skeletal muscle, it is critical for myofibrillogenesis and atrophy. However, little is known about VCP’s role(s) in the heart. Its functional diversity is determined by differential binding of distinct cofactors/adapters, which is likely disrupted during disease. VCP mutations cause multisystem proteinopathy (MSP), a pleiotropic degenerative disorder that involves inclusion body myopathy. MSP patients display progressive muscle weakness. They also exhibit cardiomyopathy and die from cardiac and respiratory failure, which are consistent with critical myocardial roles for the enzyme. Nonetheless, efficient models to interrogate VCP in cardiac muscle remain underdeveloped and poorly studied. Here, we investigated the significance of VCP and mutant VCP in the Drosophila heart. Cardiac-restricted RNAi-mediated knockdown of TER94, the Drosophila VCP homolog, severely perturbed myofibrillar organization and heart function in adult flies. Furthermore, expression of MSP disease-causing alleles engendered cardiomyopathy in adults and structural defects in embryonic hearts. Drosophila may therefore serve as a valuable model for examining role(s) of VCP in cardiogenesis and for identifying novel heart-specific VCP interactions, which when disrupted via mutation, contribute to or elicit cardiac pathology. Full article
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
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Review
Regulatory Networks that Direct the Development of Specialized Cell Types in the Drosophila Heart
J. Cardiovasc. Dev. Dis. 2016, 3(2), 18; https://doi.org/10.3390/jcdd3020018 - 12 May 2016
Cited by 5 | Viewed by 2354
Abstract
The Drosophila cardiac tube was once thought to be a simple linear structure, however research over the past 15 years has revealed significant cellular and molecular complexity to this organ. Prior reviews have focused upon the gene regulatory networks responsible for the specification [...] Read more.
The Drosophila cardiac tube was once thought to be a simple linear structure, however research over the past 15 years has revealed significant cellular and molecular complexity to this organ. Prior reviews have focused upon the gene regulatory networks responsible for the specification of the cardiac field and the activation of cardiac muscle structural genes. Here we focus upon highlighting the existence, function, and development of unique cell types within the dorsal vessel, and discuss their correspondence to analogous structures in the vertebrate heart. Full article
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
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Comment
Of Tracts, Rings, Nodes, Cusps, Sinuses, and Arrhythmias—A Comment on Szili-Torok et al.’s Paper Entitled “The ‘Dead-End Tract’ and Its Role in Arrhythmogenesis”. J. Cardiovasc. Dev. Dis. 2016, 3, 11
J. Cardiovasc. Dev. Dis. 2016, 3(2), 17; https://doi.org/10.3390/jcdd3020017 - 19 Apr 2016
Cited by 4 | Viewed by 1929
Abstract
In the review, now published as part of the special issue devoted to the development of the conduction tissues, de Vries and his colleagues discuss the potential role of the so-called “dead-end tract” as a substrate for arrhythmogenesis [1].[...] Full article
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Review
Postnatal Cardiac Autonomic Nervous Control in Pediatric Congenital Heart Disease
J. Cardiovasc. Dev. Dis. 2016, 3(2), 16; https://doi.org/10.3390/jcdd3020016 - 15 Apr 2016
Cited by 9 | Viewed by 4227
Abstract
Congenital heart disease is the most common congenital defect. During childhood, survival is generally good but, in adulthood, late complications are not uncommon. Abnormal autonomic control in children with congenital heart disease may contribute considerably to the pathophysiology of these long term sequelae. [...] Read more.
Congenital heart disease is the most common congenital defect. During childhood, survival is generally good but, in adulthood, late complications are not uncommon. Abnormal autonomic control in children with congenital heart disease may contribute considerably to the pathophysiology of these long term sequelae. This narrative review of 34 studies aims to summarize current knowledge on function of the autonomic nervous system in children with a congenital heart defect. Large scale studies that measure both branches of the nervous system for prolonged periods of time in well-defined patient cohorts in various phases of childhood and adolescence are currently lacking. Pending such studies, there is not yet a good grasp on the extent and direction of sympathetic and parasympathetic autonomic function in pediatric congenital heart disease. Longitudinal studies in homogenous patient groups linking autonomic nervous system function and clinical outcome are warranted. Full article
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Review
On the Morphology of the Drosophila Heart
J. Cardiovasc. Dev. Dis. 2016, 3(2), 15; https://doi.org/10.3390/jcdd3020015 - 12 Apr 2016
Cited by 40 | Viewed by 4429
Abstract
The circulatory system of Drosophila melanogaster represents an easily amenable genetic model whose analysis at different levels, i.e., from single molecules up to functional anatomy, has provided new insights into general aspects of cardiogenesis, heart physiology and cardiac aging, to name a [...] Read more.
The circulatory system of Drosophila melanogaster represents an easily amenable genetic model whose analysis at different levels, i.e., from single molecules up to functional anatomy, has provided new insights into general aspects of cardiogenesis, heart physiology and cardiac aging, to name a few examples. In recent years, the Drosophila heart has also attracted the attention of researchers in the field of biomedicine. This development is mainly due to the fact that several genes causing human heart disease are also present in Drosophila, where they play the same or similar roles in heart development, maintenance or physiology as their respective counterparts in humans. This review will attempt to briefly introduce the anatomy of the Drosophila circulatory system and then focus on the different cell types and non-cellular tissue that constitute the heart. Full article
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
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Review
Transcriptional Regulation of Heart Development in Zebrafish
J. Cardiovasc. Dev. Dis. 2016, 3(2), 14; https://doi.org/10.3390/jcdd3020014 - 09 Apr 2016
Cited by 16 | Viewed by 4957
Abstract
Cardiac transcription factors orchestrate the complex cellular and molecular events required to produce a functioning heart. Misregulation of the cardiac transcription program leads to embryonic developmental defects and is associated with human congenital heart diseases. Recent studies have expanded our understanding of the [...] Read more.
Cardiac transcription factors orchestrate the complex cellular and molecular events required to produce a functioning heart. Misregulation of the cardiac transcription program leads to embryonic developmental defects and is associated with human congenital heart diseases. Recent studies have expanded our understanding of the regulation of cardiac gene expression at an additional layer, involving the coordination of epigenetic and transcriptional regulators. In this review, we highlight and discuss discoveries made possible by the genetic and embryological tools available in the zebrafish model organism, with a focus on the novel functions of cardiac transcription factors and epigenetic and transcriptional regulatory proteins during cardiogenesis. Full article
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
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Review
Advances in the Study of Heart Development and Disease Using Zebrafish
J. Cardiovasc. Dev. Dis. 2016, 3(2), 13; https://doi.org/10.3390/jcdd3020013 - 09 Apr 2016
Cited by 57 | Viewed by 7273
Abstract
Animal models of cardiovascular disease are key players in the translational medicine pipeline used to define the conserved genetic and molecular basis of disease. Congenital heart diseases (CHDs) are the most common type of human birth defect and feature structural abnormalities that arise [...] Read more.
Animal models of cardiovascular disease are key players in the translational medicine pipeline used to define the conserved genetic and molecular basis of disease. Congenital heart diseases (CHDs) are the most common type of human birth defect and feature structural abnormalities that arise during cardiac development and maturation. The zebrafish, Danio rerio, is a valuable vertebrate model organism, offering advantages over traditional mammalian models. These advantages include the rapid, stereotyped and external development of transparent embryos produced in large numbers from inexpensively housed adults, vast capacity for genetic manipulation, and amenability to high-throughput screening. With the help of modern genetics and a sequenced genome, zebrafish have led to insights in cardiovascular diseases ranging from CHDs to arrhythmia and cardiomyopathy. Here, we discuss the utility of zebrafish as a model system and summarize zebrafish cardiac morphogenesis with emphasis on parallels to human heart diseases. Additionally, we discuss the specific tools and experimental platforms utilized in the zebrafish model including forward screens, functional characterization of candidate genes, and high throughput applications. Full article
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
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Review
The Early Stages of Heart Development: Insights from Chicken Embryos
J. Cardiovasc. Dev. Dis. 2016, 3(2), 12; https://doi.org/10.3390/jcdd3020012 - 05 Apr 2016
Cited by 21 | Viewed by 9137
Abstract
The heart is the first functioning organ in the developing embryo and a detailed understanding of the molecular and cellular mechanisms involved in its formation provides insights into congenital malformations affecting its function and therefore the survival of the organism. Because many developmental [...] Read more.
The heart is the first functioning organ in the developing embryo and a detailed understanding of the molecular and cellular mechanisms involved in its formation provides insights into congenital malformations affecting its function and therefore the survival of the organism. Because many developmental mechanisms are highly conserved, it is possible to extrapolate from observations made in invertebrate and vertebrate model organisms to humans. This review will highlight the contributions made through studying heart development in avian embryos, particularly the chicken. The major advantage of chick embryos is their accessibility for surgical manipulation and functional interference approaches, both gain- and loss-of-function. In addition to experiments performed in ovo, the dissection of tissues for ex vivo culture, genomic, or biochemical approaches is straightforward. Furthermore, embryos can be cultured for time-lapse imaging, which enables tracking of fluorescently labeled cells and detailed analysis of tissue morphogenesis. Owing to these features, investigations in chick embryos have led to important discoveries, often complementing genetic studies in mice and zebrafish. As well as including some historical aspects, we cover here some of the crucial advances made in understanding early heart development using the chicken model. Full article
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
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Review
The “Dead-End Tract” and Its Role in Arrhythmogenesis
J. Cardiovasc. Dev. Dis. 2016, 3(2), 11; https://doi.org/10.3390/jcdd3020011 - 05 Apr 2016
Cited by 9 | Viewed by 2455
Abstract
Idiopathic outflow tract ventricular arrhythmias (VAs) represent a significant proportion of all VAs. The mechanism is thought to be catecholamine-mediated delayed after depolarizations and triggered activity, although other etiologies should be considered. In the adult cardiac conduction system it has been demonstrated that [...] Read more.
Idiopathic outflow tract ventricular arrhythmias (VAs) represent a significant proportion of all VAs. The mechanism is thought to be catecholamine-mediated delayed after depolarizations and triggered activity, although other etiologies should be considered. In the adult cardiac conduction system it has been demonstrated that sometimes an embryonic branch, the so-called “dead-end tract”, persists beyond the bifurcation of the right and left bundle branch (LBB). Several findings suggest an involvement of this tract in idiopathic VAs (IVAs). The aim of this review is to summarize our current knowledge and the possible clinical significance of this tract. Full article
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