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The development of the cardiovascular system is a rapidly advancing area in biomedical research, now coupled with the burgeoning field of cardiac regenerative medicine. A lucid understanding of these fields is paramount to reducing human cardiovascular diseases of both fetal and adult origin. Significant progress can now be made through a comprehensive investigation of embryonic development and its genetic control circuitry. Heart Development and Regeneration, written by experts in the field, provides essential information on topics ranging from the evolution and lineage origins of the developing cardiovascular system to cardiac regenerative medicine. A reference for clinicians, medical researchers, students, and teachers, this publication offers broad coverage of the most recent advances. Volume One discusses heart evolution, contributing cell lineages; model systems; cardiac growth; morphology and asymmetry; heart patterning; epicardial, vascular, and lymphatic development; and congenital heart diseases. Volume Two includes chapters on transcription factors and transcriptional control circuits in cardiac development and disease; epigenetic modifiers including microRNAs, genome-wide mutagenesis, imaging, and proteomics approaches; and the theory and practice of stem cells and cardiac regeneration. Authored by world experts in heart development and disease New research on epigenetic modifiers in cardiac development Comprehensive coverage of stem cells and prospects for cardiac regeneration Up-to-date research on transcriptional and proteomic circuits in cardiac disease Full-color, detailed illustrations
Zebrafish (Danio rerio) are an established vertebrate model for studying heart development, regeneration and cardiotoxicity. Zebrafish embryo-larvae exposed during the temporal window of epicardium development to the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibit severe heart malformation. Thus, we sought to determine if epicardium development was affected by TCDD exposure. TCDD exposure prevents development of the epicardial progenitors (proepicardium; PE) and subsequent formation of the epicardium. Exposure to TCDD later in development, after the epicardium has formed, does not produce acute cardiac toxicity. However, in adult zebrafish, TCDD exposure prior to ventricular resection prevents cardiac regeneration; the epicardially-derived white epithelium that envelops the blood clot fails to form and cardiomyocyte proliferation is markedly reduced. It is likely that TCDD-induced inhibition of epicardium development and cardiac regeneration occur via a common mechanism. Using the embryonic zebrafish, we have identified sox9b as a downstream AHR target gene in the heart. We find that while sox9b is expressed in the myocardium, it is not expressed in the affected epicardial cells or progenitors. TCDD exposed zebrafish embryos had significantly reduced levels of cardiac sox9b during epicardium development. Furthermore, we found manipulation of sox9b expression could phenocopy most of the effects of TCDD at the heart. Loss of sox9b prevented the formation of epicardial progenitors comprising the PE on the pericardial wall, and prevented the formation and migration of the epicardium around the heart. Zebrafish lacking sox9b showed pericardial edema, heart elongation, reduced blood circulation and lacked endocardial valve cushions and leaflets. Furthermore, sox9b mRNA injection prior to TCDD exposure rescued PE formation, but the epicardium failed to form. Myocardial contractility remained severely affected in sox9b mRNA injected TCDD-treated fish. This led us to investigate the role of myocardial contractility during epicardium formation. Lack of heart contractility resulted in a phenotype analogous to our sox9b rescue experiments; the PE formed but failed to migrate and form the epicardium. These experiments demonstrate myocardial contractility is required for PE cell migration and epicardium formation. Together, zebrafish epicardium development requires sox9b and normal cardiac contractility, which in our model, are severely affected by TCDD.
The developing heart is the first functional organ, and its proper formation and function is essential for life. This volume compiles the exciting new advances that have been made in understanding the regulation of heart development, the genes and pathways involved, and the impact these have in heart disease. A stellar collection of scientists tackles an important facet of heart development, providing a comprehensive set of reviews. Cutting-edge science Authority of contributors Exciting field of research
The term “Translational Research” reflects today’s integration of basic research (“bench”) findings with the clinical practice of medicine, and in a wider scope the application of results from the individual patient (“bedside”) to entire populations for the improvement of public health. This book offers future researchers a stimulus in many aspects of cardiovascular research, so as to promote their interest in future fields of cardiovascular disease, diagnosis and treatment. Introduction to Translational Cardiovascular Research discusses the fundamental and important aspects of the topic. It describes the renin-angiotensin-aldosterone system, the beta adrenergic receptors and the hypothalamic-pituitary-adrenal axis, while covering genetic polymorphisms both generally and specifically as regards the vascular endothelium and the use of microRNAs. As such, this book will be relevant to young physicians, nurses and other scientists engaged in the clinical cardiovascular field who want to added research-oriented dimension to their efforts towards better understanding and practicing of medicine. It also aims to attract young basic researchers who want to develop a better comprehension of the organism as a whole, man or animal, that they are investigating.
To achieve cardiac regeneration using pluripotent stem (iPS) cells, researchers must understand iPS cell generation methods, cardiomyocyte differentiation protocols, cardiomyocyte characterization methods, and tissue engineering. This book presents the current status and future possibilities in cardiac regeneration using iPS cells. Written by top researchers who present new data in these fields, this book reviews cardiac cell therapy for ischemic heart disease and explores in vitro generation of efficacious platelets from iPS cells. It also discusses modeling arrhythmogenic heart disease with patient-specific induced pluripotent stem cells.
This work encapsulates the uses of miRNA across stem cells, developmental biology, tissue injury and tissue regeneration. In particular contributors provide focused coverage of methodologies, intervention and tissue engineering. Regulating virtually all biological processes, the genome’s 1048 encoded microRNAs appear to hold considerable promise for the potential repair and regeneration of tissues and organs in future therapies. In this work, 50 experts address key topics of this fast-emerging field. Concisely summarizing and evaluating key findings emerging from fundamental research into translational application, they point to the current and future significance of clinical research in the miRNA area. Coverage encompasses all major aspects of fundamental stem cell and developmental biology, including the uses of miRNA across repair and regeneration, and special coverage of methodologies and interventions as they point towards organ and tissue engineering Multi-colour text layout with 150 colour figures to illustrate important findings Take home messages encapsulate key lessons throughout text Short chapters offer focused discussion and clear ‘voice’

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