Download or read book Investigating mechanisms of angiogenesis in health and disease using zebrafish models written by Zaheer Ali and published by Linköping University Electronic Press. This book was released on 2018-12-07 with total page 49 pages. Available in PDF, EPUB and Kindle. Book excerpt: Angiogenesis, the growth of blood vessels from an existing vasculature, can occur by sprouting from preexisting vessels or by vessel splitting (intussusception). Pathological angiogenesis drives choroidal neovascularization (CNV) in age related macular degeneration (AMD) which is commonly restricted under the retinal pigment epithelium (RPE), called occult CNV, but may also involve vessels penetrating through the RPE into the sub-retinal space. Pathological vessels are poorly developed, insufficiently perfused and highly leaky, phenotypes that are considered to drive disease progression and lead to poor prognosis. Currently, a number of anti-angiogenic drugs exists, the majority of which target vascular endothelial factor (VEGF), but although they often are highly beneficial for treating eye diseases in the short-term, they are generally of limited efficacy in other diseases such as cancer, and also have poorer efficacy when used for treatment of eye diseases in the long-term. A better understanding of the mechanisms underlying pathological angiogenesis can generate new targets for treatment leading to development of better drugs for cancer and retinopathies, but perhaps also other angiogenesis-dependent diseases, in the future. In this thesis mechanisms involved in developmental angiogenesis or pathological angiogenesis in the choroid, cornea or melanoma was identified. These findings highlight the need to further elaborate our knowledge related to angiogenesis in different tissues/conditions for a more targeted, and potentially effective treatment of diseases in the future. In paper I, we for the first time identified the choriocapillaries (CCs) in adult zebrafish and found that occult CNV could be induced by exposing the fish to severe hypoxia. Interestingly, we found that occult CNV relied on intussusception, involving not only de novo generation of intussusceptive pillars but also a previously poorly understood mechanism called pillar splitting. This involved HIF-VEGF-VEGFR2 signaling and evidence that this also occurred in both rats and humans suffering from AMD suggested that the mechanism was conserved and clinically relevant. In contrast, we found in paper II that the development of CCs in the zebrafish relies on sprouting angiogenesis, involve continuous remodeling, and delayed maturation of the vasculature in 2D. The initial development was found to occur by a unique process of tissuewide synchronized vasculogenesis. As expected, VEGFA via VEGFR2 was also critical for the development of these vessels in the zebrafish embryo, but surprisingly this was independent on hypoxia-inducible factor (HIF)-1. Inflammatory nuclear factor-kB (NF-kB) signaling is involved in the progression of angiogenesis, but this signaling pathway has mainly been studied in the inflammatory cells and the role of NF-kB in the endothelial cells during angiogenesis is poorly understood. In paper III, we found that blocking NF-kB signaling using a specific IKK2 blocker IMD0354, specifically blocks pathological as well as developmental angiogenesis by targeting endothelial cell NF-kB signaling in the endothelial cells. Using a rat model for suture-induced corneal neovascularization, IMD0354 treatment lead to reduced production of inflammatory C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 5 (CXCL5) and VEGF, and thereby reduced pathological corneal angiogenesis in this model. Using the zebrafish tumor xenograft model in paper IV, we found an association between Microphthalmia associated transcription factor (MITF) and pigment epithelium derived factor (PEDF), which was involved in pathological tumor angiogenesis and metastasis. Similarly, in paper V we used zebrafish transplantation models to study and investigate the use of biocompatible polymers for the delivery of pro-angiogenic FGF-2 as a potential treatment strategy for ischemic diseases such as myocardial infarction (MI). Conclusively, this thesis provides new insights into diverse fields of angiogenic assays using zebrafish, and reveals new mechanisms of angiogenesis in health and disease. This work will hopefully provide a foundation for further studies into occult CNV related to AMD, a process that has not been possible to study previously in pre-clinical models. In addition, zebrafish xenograft or other transplantation models used in this work will likely be important to study cancer biology and to develop more attractive pharmaceutical preparations based on biocompatible hydrogels formulated as microspheres in the future.
Download or read book Angiogenesis Assays written by Carolyn A. Staton and published by John Wiley & Sons. This book was released on 2007-01-11 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: Angiogenesis, the development of new blood vessels from the existing vasculature, is essential for physiological growth and over 18,000 research articles have been published describing the role of angiogenesis in over 70 different diseases, including cancer, diabetic retinopathy, rheumatoid arthritis and psoriasis. One of the most important technical challenges in such studies has been finding suitable methods for assessing the effects of regulators of eh angiogenic response. While increasing numbers of angiogenesis assays are being described both in vitro and in vivo, it is often still necessary to use a combination of assays to identify the cellular and molecular events in angiogenesis and the full range of effects of a given test protein. Although the endothelial cell - its migration, proliferation, differentiation and structural rearrangement - is central to the angiogenic process, it is not the only cell type involved. the supporting cells, the extracellular matrix and the circulating blood with its cellular and humoral components also contribute. In this book, experts in the use of a diverse range of assays outline key components of these and give a critical appraisal of their strengths and weaknesses. Examples include assays for the proliferation, migration and differentiation of endothelial cells in vitro, vessel outgrowth from organ cultures, assessment of endothelial and mural cell interactions, and such in vivo assays as the chick chorioallantoic membrane, zebrafish, corneal, chamber and tumour angiogenesis models. These are followed by a critical analysis of the biological end-points currently being used in clinical trials to assess the clinical efficacy of anti-angiogenic drugs, which leads into a discussion of the direction future studies should take. This valuable book is of interest to research scientists currently working on angiogenesis in both the academic community and in the biotechnology and pharmaceutical industries. Relevant disciplines include cell and molecular biology, oncology, cardiovascular research, biotechnology, pharmacology, pathology and physiology.
Download or read book VEGF mediated vascular functions in health and disease written by Ziquan Cao and published by Linköping University Electronic Press. This book was released on 2015-04-24 with total page 135 pages. Available in PDF, EPUB and Kindle. Book excerpt: Angiogenesis is essential for physiological processes including embryonic development, tissue regeneration, and reproduction. Under various pathological conditions the same angiogenic process contribute to the onset, development, and progression of many human diseases including cancer, diabetic complications, ocular disease, chronic inflammation and cardiovascular disease. Vascular endothelial growth factor (VEGF) is a key angiogenic factor for physiological and pathological angiogenesis. In addition to its strong angiogenic activity, VEGF also potently induces vascular permeability, often causing tissue edema in various pathological tissues. VEGF transduces its vascular signal through two tyrosine kinase receptors-VEGFR1 and VEGFR2, the latter being a functional receptor that mediates both angiogenic and vascular permeability effects. To study physiological and pathological functions of VEGF, we developed novel zebrafish disease models that permit us to study hypoxia-induced retinopathy and cancer metastasis processes. We have also administered anti-VEGF and anti-VEGFR specific antibodies to healthy mice to study the homeostatic role of VEGF in the maintenance of vascular integrity and its functions in various tissues and organs. Finally, using a zebrafish model, we evaluated if VEGF expression is regulated by circadian clock genes. In paper I, we developed protocols that create hypoxia-induced retinopathy in adult zebrafish. Adult fli1:EGFP zebrafish were placed in hypoxic water for 3-10 days with retinal neovascularization being analyzed using confocal microscopy. This model provides a unique opportunity to kinetically study the development of retinopathy in adult animals using non-invasive protocols and to assess the therapeutic efficacy of orally administered anti-angiogenic drugs. In paper II, we developed a zebrafish metastasis model to dissect the complex events of hypoxia-induced tumor cell invasion and metastasis in association with angiogenesis at the single-cell level. In this model, fluorescent DiI-labeled human or mouse tumor cells were implanted into the perivitelline cavity of 48-hour-old zebrafish embryos, which were subsequently placed in hypoxic water for 3 days. Tumor cell invasion, metastasis and pathological angiogenesis were analyzed using fluorescent microscopy in the living fish. The average experimental time for this model is 7 days. Our protocol offers an opportunity to study molecular mechanisms of hypoxia-induced cancer metastasis. In paper III, we show that systemic delivery of an anti-VEGF or an anti-VEGF receptor (VEGFR)-2 neutralizing antibody cause global vascular regression in mice. Among all examined tissues, the vasculature in endocrine glands, intestinal villi, and the uterus are most affected in response to VEGF or VEGFR-2 blockades. Pro-longed anti-VEGF treatment resulted in a significant decrease in the circulating levels of the predominant thyroid hormone, free thyroxine, but not the minimal isoform of triiodothyronine, suggesting that chronic anti-VEGF treatment impairs thyroid function. These findings provide structural and functional bases of anti-VEGF-specific druginduced side effects in relation to vascular changes in healthy tissues. In paper IV, we show that disruption of the circadian clock by constant exposure to light coupled with genetic manipulation of key genes in the zebrafish led to impaired developmental angiogenesis. A bmal1-specific morpholino inhibited developmental angiogenesis in zebrafish embryos without causing obvious nonvascular phenotypes. Conversely, a period2 morpholino accelerated angiogenic vessel growth, suggesting that Bmal1 and Period2 display opposing angiogenic effects. These results offer mechanistic insights into the role of the circadian clock in regulation of developmental angiogenesis, and our findings may be reasonably extended to other types of physiological or pathological angiogenesis. Overall, the results in this thesis provide further insight to angiogenic mechanistic properties in tissues and suggest possible novel therapeutic targets for the treatment of various angiogenesis-dependent diseases.
Download or read book Endothelial Dynamics in Health and Disease written by Jaap Diederik Van Buul and published by Frontiers Media SA. This book was released on 2021-01-06 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Angiogenesis and Vascularisation written by Józef Dulak and published by Springer Science & Business Media. This book was released on 2014-02-10 with total page 414 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book presents the overview of the current knowledge in some fields of vascular biology, addressing cellular and molecular aspects of blood-vessel formation and their role in health and disease. The major factors involved in the formation of blood vessels are presented by scientists actively involved in this area of research. Special emphasis is put on the presentation of various molecular mechanisms not addressed in similar works to date. The book is divided into three parts. The first part describes the cells and mediators in angiogenesis. The significance of various populations of potential endothelial progenitors is particularly highlighted. The chapters of the second part focus on molecular mechanisms, with special emphasis on the role of hypoxia, gasotransmitters and reactive oxygen species as well as microRNAs in regulation of angiogenic processes. In the third part, the pathological aspects of disturbed – aggravated or impaired – vascularization are discussed and new modalities for potential therapies are presented. The book is intended for scientists and PhD students in the fields of vascular biology and cancer research. It may be of interest for medical professionals in the fields of cardiovascular disease, diabetes, oncology and rheumatoid arthritis.
Download or read book Scientific Frontiers in Developmental Toxicology and Risk Assessment written by National Research Council and published by National Academies Press. This book was released on 2000-12-21 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt: Scientific Frontiers in Developmental Toxicology and Risk Assessment reviews advances made during the last 10-15 years in fields such as developmental biology, molecular biology, and genetics. It describes a novel approach for how these advances might be used in combination with existing methodologies to further the understanding of mechanisms of developmental toxicity, to improve the assessment of chemicals for their ability to cause developmental toxicity, and to improve risk assessment for developmental defects. For example, based on the recent advances, even the smallest, simplest laboratory animals such as the fruit fly, roundworm, and zebrafish might be able to serve as developmental toxicological models for human biological systems. Use of such organisms might allow for rapid and inexpensive testing of large numbers of chemicals for their potential to cause developmental toxicity; presently, there are little or no developmental toxicity data available for the majority of natural and manufactured chemicals in use. This new approach to developmental toxicology and risk assessment will require simultaneous research on several fronts by experts from multiple scientific disciplines, including developmental toxicologists, developmental biologists, geneticists, epidemiologists, and biostatisticians.
Download or read book Tumour Angiogenesis written by R. John Bicknell and published by . This book was released on 1997 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumour Angiogenesis is the first comprehensive book to cover all areas of this rapidly expanding research area. Each chapter is written by world experts in the field and topics covered include in vivo models, mechanisms, inhibition, and the role of macrophages, cytokines, proteases,extracellular matrix components, nitric oxide, prostanoids and oncogenes/tumour suppressor genes in angiogenesis. Other chapters examine the role of specific growth factors in angiogenesis - these include vascular endothelial growth factor, the basic fibroblast growth factor family, transforminggrowth factor-beta, tumour necrosis factor-alpha, platelet-derived endothelial cell growth factor/thymidine phosphorylase and pleiotrophin and related molecules. Clinical issues are addressed in chapters that deal with the prognostic and predictive value of tumour microvessel density and thetherapeutic significance of microregional blood flow. The two final chapters examine the feasibility of targeting tumour vasculature using either antibodies or gene therapy.
Download or read book Targeting Neuroinflammation in Central Nervous System Disorders Uncovering Mechanisms Pharmacological Targets and Neuropharmaceutical Developments written by Mariela Fernanda Perez and published by Frontiers Media SA. This book was released on 2022-01-20 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Angiogenesis in Adipose Tissue written by Yihai Cao and published by Springer Science & Business Media. This book was released on 2013-09-05 with total page 374 pages. Available in PDF, EPUB and Kindle. Book excerpt: Angiogenesis has recently played a critical role in regulation of adipose tissue expansion and regression. Like most other tissues in the body, adipose expansion and regression is accompanied by alteration of blood vessel density and structures. The vascular alteration plays an active role in regulation of adipose tissue size and functions. Targeting blood vessels in the adipose tissue have demonstrated to be a novel approach for possibly treatment of cancer, obesity and other metabolic diseases. This book provides the most updated information on this type research and discusses future opportunities for therapy..
Download or read book Anti Angiogenesis Strategies in Cancer Therapies written by Shaker Mousa and published by Academic Press. This book was released on 2016-11-28 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt: Anti-angiogenesis Strategies in Cancer Therapeutics provides a detailed look at the current status and future directions in the discovery and development of novel anti-angiogenesis strategies in oncology. This book highlights the different mechanisms involved in the modulation of angiogenesis, including inflammation, thrombosis, and microRNA, and shows how nanotechnology can further enhance the potential of existing and new anti-angiogenesis approaches. Written for industry scientists, researchers, oncologists, hematologists, and professors and students in the field, this comprehensive book covers all aspects of anti-angiogenesis strategies and their differences. Covers important preclinical models and clinical trials in the discovery and development of novel anti-angiogenesis agents Reviews FDA-approved anti-angiogenesis agents Illustrates the value of nanotechnology in improving the utility of anti-angiogenesis agents Offers insight into the development of novel anti-angiogenesis agents and future direction in this area
Download or read book Intracerebral Hemorrhage Research written by John Zhang and published by Springer Science & Business Media. This book was released on 2011-07-05 with total page 420 pages. Available in PDF, EPUB and Kindle. Book excerpt: The volume includes 75 papers which were presented at the Third International Conference on Intracerebral Hemorrhage, held in Rancho Mirage, California, in March 2010. The topics treated include animal models, pathophysiology of cerebral hemorrhage, experimental treatment for cerebral hemorrhage, cerebral hemorrhage clinical manifestations, prognosis of cerebral hemorrhage, and clinical management. The articles represent the recent advances in hemorrhagic brain injury research presented by highly respected laboratories around the world.
Download or read book Establishing and Maintaining Cell Polarity written by Benjamin Lin and published by Frontiers Media SA. This book was released on 2021-12-22 with total page 125 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Vascular Development written by Derek J. Chadwick and published by John Wiley & Sons. This book was released on 2007-08-20 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: The formation of blood vessels is an essential aspect of embryogenesis in vertebrates. It is a central feature of numerous post-embryonic processes, including tissue and organ growth and regeneration. It is also part of the pathology of tumour formation and certain inflammatory conditions. In recent years, comprehension of the molecular genetics of blood vessel formation has progressed enormously and studies in vertebrate model systems, especially the mouse and the zebrafish, have identified a common set of molecules and processes that are conserved throughout vertebrate embryogenesis while, in addition, highlighting aspects that may differ between different animal groups. The discovery in the past decade of the crucial role of new blood vessel formation for the development of cancers has generated great interest in angiogenesis (the formation of new blood vessels from pre-existing ones), with its major implications for potential cancer-control strategies. In addition, there are numerous situations where therapeutic treatments either require or would be assisted by vasculogenesis (the de novo formation of blood vessels). In particular, post-stroke therapies could include treatments that stimulate neovascularization of the affected tissues. The development of such treatments, however, requires thoroughly understanding the developmental properties of endothelial cells and the basic biology of blood vessel formation. While there are many books on angiogenesis, this unique book focuses on exactly this basic biology and explores blood vessel formation in connection with tissue development in a range of animal models. It includes detailed discussions of relevant cell biology, genetics and embryogenesis of blood vessel formation and presents insights into the cross-talk between developing blood vessels and other tissues. With contributions from vascular biologists, cell biologists and developmental biologists, a comprehensive and highly interdisciplinary volume is the outcome.
Download or read book Handbook of Vascular Biology Techniques written by Mark Slevin and published by Springer. This book was released on 2016-10-13 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: A wide range of research methods for the study of vascular development, from basic laboratory protocols to advanced technologies used in clinical practice, are covered in this work. A range of methodologies such as molecular imaging platforms and signalling analysis, along with tumour models are collated here. Four sections explore in vitro techniques, in vivo and ex vivo manipulations, imaging and histological analysis and other novel techniques in vascular biology. Readers will discover basic methodologies used for analysis of endothelial cell growth in vitro, including co-culture models of vessel formation. Authors also explore isolation and purification of cells and methods for analysis of data and visualization of localized vasculature with modern imaging platforms. Both animal models and human disease are covered in this work. Each chapter contains helpful sections on trouble shooting, additional notes and links, supporting the reader to carry out protocols. This book will appeal to students, researchers and medical professionals working in all vascular-linked fields such as cardio- and cerebrovascular, cancer and dementia.
Download or read book Zebrafish Model for Biomedical Research written by Prasan R. Bhandari and published by Springer Nature. This book was released on 2022-05-30 with total page 493 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides the latest information on the significance of zebrafish as an ideal model for researching the biomedical field, with references. This book also focused on the evidence of zebrafish as a model in cardiovascular, neurologic, psychiatric and metabolic research. In addition, the book also includes the research carried out on zebrafish in hepatic, renal, ophthalmic, and ENT related areas. Contributed chapters come from the most prominent laboratories working in this field, which provides a unique perspective on zebrafish models from a wide spectrum of the research community. In addition, the book offers a detailed analysis of the most current research in the area for specific zebrafish models including specific research in the area of skin disorders, endocrine diseases, nutritional disorders, gastrointestinal, hematological disorders and cancer. The compilation of chapters in the volume culminates into a comprehensive and definitive text on zebrafish and its suitability for modeling various diseases, providing a critical resource on the potential attributes of the zebrafish as a pharmacological model. In terms of scope, this book is a useful tool for young researchers, professors and pharmaceutical scientists for understanding the significance of zebrafish as an emerging pharmacological model that can significantly aid in the process of drug discovery and development.
Download or read book Nutraceuticals and Natural Product Derivatives written by Mohammad Fahad Ullah and published by John Wiley & Sons. This book was released on 2019-03-06 with total page 450 pages. Available in PDF, EPUB and Kindle. Book excerpt: Introduces readers to the growing applications of nutraceuticals and other natural product derivatives This comprehensive book presents a prophylactic and therapeutic approach to chronic disease prevention strategy by highlighting the translational potential of plant-derived dietary and non-dietary factors from epidemiological, laboratory, and clinical studies. It also shares the experiences of highly reputed experts working in the area of phytomedicine and nutraceutical agents in chemoprevention, to promote the significance of natural products and dietary factors as an elite priority for containing chronic diseases in the human population. Nutraceuticals and Natural Product Derivatives: Disease Prevention & Drug Discovery starts by examining natural food sources for the control of glycemia and the prevention of diabetic complications. It then looks at the anti-aging effects of sulfur-containing amino acids and nutraceuticals, and the potential of garcinia fruits to combat metabolic syndrome. Other topics covered include honey- and propolis-mediated regulation of protein networks in cancer cells; recent trends in drug discovery against Alzheimer’s disease; the therapeutic potential of metalloherbal nanoceuticals; and much more. Offers an alternative, natural approach to the prevention of chronic diseases Emphasizes the potential of plant-derived dietary and non-dietary factors from epidemiological, laboratory, and clinical studies Features contributions from world-renowned experts in the field of phytomedicine and nutraceutical agents in chemoprevention Includes prevention strategies in normal/risk populations through routine inclusion of specific dietary regimens and as therapeutic strategy for better management through adjuvant interventions with conventional treatment protocols Nutraceuticals and Natural Product Derivatives: Disease Prevention & Drug Discovery will appeal to graduate students and professionals in cell and molecular biology, translational research, pharmacology/drug discovery, medicinal chemistry, and clinical nutrition.
Download or read book The Zebrafish Disease Models and Chemical Screens written by H. William Detrich and published by Academic Press. This book was released on 2011-09-23 with total page 591 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume of Methods in Cell Biology is the 3e, and provides comprehensive compendia of laboratory protocols and reviews covering all the new methods developed since 2004. This new volume on Disease Models and Chemical Screens, covers two rapidly emerging and compelling applications of the zebrafish. Details state-of-the art zebrafish protocols, delineating critical steps in the procedures as well as potential pitfalls This volume concentrates on Disease Models and Chemical Screens
