Angiogenesis In Health And Disease

Angiogenesis describes the formation of new blood vessels, which arise as outgrowths from existing vessels. In many physiological processes such as ovulation and wound healing angiogenesis is involved for a relatively short time. Otherwise under normal physiological conditions in the adult organism angiogenesis is an extremely slow process. By contrast in certain disease states such as diabetic retinopathy, arthritis, chronic inflammation, hemangiomas, etc., angiogenesis persists and contributes to the pathology of these disease states. Some 50 such "angiogenic diseases" have been described where angiogeneSiS is involved. Also in tumor growth and metastasis angiogenesis is an essential process and precedes neoplastic transformation. Hence, angiogenesis could become an important diagnostic tool and a target for developing therapeutic agents. This book contains the proceedings of the NATO Advanced Study Institute on "Angiogenesis in Health and Disease" held in Porto Hydra, Greece, from June 16-27, 1991. This meeting was a comprehensive review of endothelial cell biology and endothelial cell phenotypic and functional heterogeneity in relation to angiogenesis under physiological and pathological conditions. Numerous in vitro and in vivo models were presented, which are used to study angiogenesis at the molecular and cellular levels and to evaluate chemical compounds or naturally occuring substances for their effect on angiogenesis. The presentations and discussions at this meeting provided an opportunity for the basic science and the clinical disciplines to meet, exchange information and provide future research directions for many investigators engaged in the study of angiogenesis.

This book is about “Angiogenesis”. A process in which new vasculature is formed from pre-existing capillaries. Angiogenesis process is associated with the proliferation and growth of both physiologically normal and neoplastic tissues, through the formation of vascular supply, essential for delivering growth requirements such as oxygen and nutrients. The book describes more than 100 genes and their key regulatory functions in the context of normal healthy condition, disease and malignancy, cancer proliferation and progression. New insights into the role of angiogenesis and the therapeutic inhibition of its regulators are investigated, due to the great potential for exploitation in the development of a novel treatment for cancer. New scientists, junior researchers and biomedical science students will find this book an invaluable introductory reference to their insight about angiogenesis and angiogenic role of more than 100 angiogenes and their role in healthy, disease and malignant conditions.

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.

Outlines strategies for stimulating capillary formation in hypoxia and ischemia and inhibiting it in cancer, diabetes, and chronic inflammation. This state-of-the-science reference highlights recent progress in the ways to promote formation of new blood vessels in ischemic/hypoxic tissue and the means to stifle capillary growth and development in solid tumors, diabetic retinopathy, and chronic immuno/inflammatory disorders such as rheumatoid arthritis and psoriasis. Emphasizes practical clinical applications derived from the latest angiogenesis research. Written by over 80 leading international experts, Angiogenesis in Health and Disease examines new angiogenic regulators such as angiopoietins and TIE-receptors describes angiogenic genes such as thymosine B-4, EDG-1, and ARNT proteins analyzes the role of vascular endothelial growth factor (VEGF) in capillary sprouting investigates behaviors of endogenous agents of angiogenesis, including cytokines, hormones, chemokines, and peptide and hematopoietic growth factors explores mechanisms for ameliorating or preventing vascular occlusive disease by induction of collateral artery growth explains differences in conditions that prompt angiogenesis and arteriogenesis reviews transgenic and knock-out mice, receptor protein mutations, and other emerging technologies evaluates angiogenic inhibitors such as angiostatin and endostatin and more! Containing over 3000 references, tables, drawings, and photographs, Angiogenesis in Health and Disease deserves a prominent place on the bookshelves of cardiologists, oncologists, physiologists, hematologists, molecular and cell biologists, biochemists, pharmacologists, rheumatologists, vascular surgeons, and upper-level undergraduate, graduate, and medical school students in these disciplines.

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.

Outlines strategies for stimulating capillary formation in hypoxia and ischemia and inhibiting it in cancer, diabetes, and chronic inflammation. This state-of-the-science reference highlights recent progress in the ways to promote formation of new blood vessels in ischemic/hypoxic tissue and the means to stifle capillary growth and development in solid tumors, diabetic retinopathy, and chronic immuno/inflammatory disorders such as rheumatoid arthritis and psoriasis. Emphasizes practical clinical applications derived from the latest angiogenesis research. Written by over 80 leading international experts, Angiogenesis in Health and Diseaseexamines new angiogenic regulators such as angiopoietins and TIE-receptors describes angiogenic genes such as thymosine B-4, EDG-1, and ARNT proteins analyzes the role of vascular endothelial growth factor (VEGF) in capillary sprouting investigates behaviors of endogenous agents of angiogenesis, including cytokines, hormones, chemokines, and peptide and hematopoietic growth factors explores mechanisms for ameliorating or preventing vascular occlusive disease by induction of collateral artery growth explains differences in conditions that prompt angiogenesis and arteriogenesis reviews transgenic and knock-out mice, receptor protein mutations, and other emerging technologies evaluates angiogenic inhibitors such as angiostatin and endostatin and more!Containing over 3000 references, tables, drawings, and photographs, Angiogenesis in Health and Disease deserves a prominent place on the bookshelves of cardiologists, oncologists, physiologists, hematologists, molecular and cell biologists, biochemists, pharmacologists, rheumatologists, vascular surgeons, and upper-level undergraduate, graduate, and medical school students in these disciplines.

Angiogenesis is a highly complex phenomenon where new blood vessels are formed for the supply of oxygen and nutrients in different organs of the body. It plays a critical role in both physiological processes such as growth and development as well as pathological processes including cancer and different types of tumors. Angiogenesis is also essential for the regeneration and survival of cells in several disease conditions such as ischemic heart disease (myocardial infarction), atherosclerosis, brain injury (stroke) and diabetes. Since the mechanisms of angiogenesis are organ specific and differ among various diseases, it is proposed to devote one section of this book to the development of angiogenesis in some selected diseases such as cancer, ischemic heart disease, atherosclerosis, diabetes and stroke. It is pointed out that extensive research work in this regard has been carried out in the area of cancer and heart disease, whereas relatively less attention has been paid to studying angiogenesis in other disease conditions.

New Frontiers in Angiogenesis is a fresh and unconventional look at the field of angiogenesis. It focuses on provocative and cutting-edge topics in the field of angiogenesis. Each chapter will take the reader along on a journey into uncharted territories of angiogenesis. The volume starts with a comprehensive overview of the field and continues with topics that have been minimally explored. The topics deal with dynamics of vasculogenesis using imaging techniques, bone marrow-derived endothelial cell precursors as potential therapeutic tools, regulation of post-angiogenic vessel regression, vascular mimicry, design and construction of artificial vessels, bioengineering of angiogenesis, and lymphangiogenesis recapitulating angiogenesis in health and disease states. Each chapter is written by leading experts of the subjects. It is hoped that this volume will challenge all of us interested in the field of angiogenesis and cardiovascular biology, in particular those in academia and industries, to think "outside the box" and explore angiogenesis from a fresh angle. It is hoped that New Frontiers in Angiogenesis is thought provoking and serve as a road map for discovering new findings to help betterments of human health.