Mohan K. Raizada - Böcker

Recent progress in recombinant DNA technology and the availability of a number of nonpeptide subtype-specific receptor antagonists and of specific antibodies to components of prorenin-renin-angiotensin system (PRAS) have led to rapid advances in the under­ standing of the multifaceted role of angiotensin II, classically known as a peptide hormone of cardiovascular homeostasis. Accumulating evidence sug­ responsible for the regulation gests that, in addition to its role in salt and water metabolism, PRAS may control other physiological functions including neurosecretion, cellular proliferation, hypertrophy and/or differentiation, angiogenesis and gonadal function. At the same time, it is becoming evident that the specialized functions of endocrine glands are not only regulated by trophic hormones but also by locally produced paracrine/autocrine factors. The concept is emerging that tissue PRAS is one such locally active regulatory system. With more and more reproductive and endocrine organs being added to the list of tissues that contain a local tissue PRAS, questions are being raised by the reproductive biologists and endocrinologists as to the role of such systems in the tissues of their interest. On the other hand, the cardiovascular and renovascular physiologists are wondering about the relevance of PRAS in various peripheral tissues compared to those of the classical cardiovascular organs. It appeared, therefore, that the time was ripe for a meeting to consider a merger of interest in these two important but heretofore distinct areas of physiology.

Scientific advances over the past two decades have afforded unprecedented oppor­ tunities to understand the structure and function of receptors, receptor-ligand interactions, and receptor signaling. The extent ofprogress in this area is underscored by the recent Nobel Prize for Medicine and Physiology to Alfred Gilman and Martin Rodbell, both of whose work in understanding receptorlG-protein interactions has redefined the way in which we think of how hormones and neurochemicals exert their activity on cellular function. This book is replete with examples of current research approaches to help us better understand the cellular roles in which the renin-angiotensin system and the angiotensin receptors participate. Clearly, defining the structure of angiotensin receptor subtypes is an important first step in cJarifying the mechanisms by which these receptors take part in cellular function. However, the chapters within this book range far beyond structural studies and encompass research on tissue specific expression of the angiotensin receptor subtypes, the genetic regulation ofthese receptors, and the unique function ofvarious angiotensin subtypes in different organ systems, such as the brain, the reproductive system, adipose tissue, the heart, and the kidneys.

Cellular and Molecular Biology of the Renin-Angiotensin System provides the first review and update of the state-of-the-art cellular and molecular aspects of the renin-angiotensin system. The book presents detailed analyses from world experts on each component of this system, including future directions. Topics range from angiotensin II receptor subtypes to processing of renin to the use of transgenic animal models for studying the role of this system in hypertension.Cellular and Molecular Biology of the Renin-Angiotensin System is essential reading for physiologists of the renin-angiotensin system, endocrinologists, cardiovascular specialists, renal physiologists, and neurobiologists.

The study of the insulin-like growth factor (IGF) family has become an exciting area of investigation. Initially, this family consisted of ligands (insulin, IGF-I and IGF-m and receptors (the insulin receptor, the type I or IGF-I receptor and the type II or IGF-IYM-6-P receptor). Subsequently, it was discovered that six specific binding proteips (lGFBPs 1-6) playa major role in the actions of this growth factor family. In addition, there are now more potential receptors when one considers the possible roles of the insulin-receptor related receptor (IRR) and hybrid receptor dimers composed of insulin and IGF-I receptor (half-receptors). Another important aspect of this area of research is the realization that the IGFs are not only essential for normal growth and development but, in addition play an important role in the normal specialized function(s) of all tissues of the body, including the nervous system, skeleton, reproductive system, kidney, and the immune system, to name but a few. The development of recombi!tant human IGF-I for clinical testing has been a major breakthrough for investigators. Potential uses include wound healing, reversal of catabolic states, diabetes, bone remodeling, recovery from acute renal failure and many others. will determine both its use and its potential hazards.

An essential element in the development and functional integrity of all organisms is intercellular communication. This is achieved by the secretion of soluble messenger molecules which subsequently interact with receptor-effector pathways in the responsive cells. Hormones are traditionally defined as chemical messengers synthesized by endocrine glands. Unlike hormones produced by endocrine glands, growth factors are hormone-related substances produced by many tissues and play an important role in controlling growth and development. While the exact physiological roles of growth factors have yet to be elucidated, they play important roles in the regulation of cellular proliferation and/or differentiation during ontogenesis, growth and differentiation. During recent years there has been a substantial increase in research related to peptide growth factors, their receptors, and modes of action. With the discovery and characterization of numerous growth factors, it became clear that these growth factors had multiple features in common with classic hormones as well as with oncogenes. Furthermore, there are distinct families of growth factors based either on structural or functional similarities.

This volume addresses a fundamental puzzle in biology and medicine, namely, how does tissue develop, repair and replace itself. The answer appears to lie in growth factors and their regulation. To thrive and survive we need growth factors and this book concentrates on two factors that are related to growth hormone. Growth hormone does not act directly on all tissues, but mediates many of its actions through the release of insulin-like growth factors from the liver. The growth factors were originally called somatomedins by McConaghey and Sledge (1), who discovered that they mediated growth-like effects of growth hormone. However, the factors were purified on the basis of their insulinomimetic actions on fat and muscle and it is their relationship to the insulin family of pep tides that now gives them their name (2,3) of insulin-like growth factors (IGFs). They mediate the actions of. growth hormone on the proteoglycan synthesis of cartilage and produce mitogenic effects in fibroblast cultures.

Recent progress in recombinant DNA technology and the availability of a number of nonpeptide subtype-specific receptor antagonists and of specific antibodies to components of prorenin-renin-angiotensin system (PRAS) have led to rapid advances in the under­ standing of the multifaceted role of angiotensin II, classically known as a peptide hormone of cardiovascular homeostasis. Accumulating evidence sug­ responsible for the regulation gests that, in addition to its role in salt and water metabolism, PRAS may control other physiological functions including neurosecretion, cellular proliferation, hypertrophy and/or differentiation, angiogenesis and gonadal function. At the same time, it is becoming evident that the specialized functions of endocrine glands are not only regulated by trophic hormones but also by locally produced paracrine/autocrine factors. The concept is emerging that tissue PRAS is one such locally active regulatory system. With more and more reproductive and endocrine organs being added to the list of tissues that contain a local tissue PRAS, questions are being raised by the reproductive biologists and endocrinologists as to the role of such systems in the tissues of their interest. On the other hand, the cardiovascular and renovascular physiologists are wondering about the relevance of PRAS in various peripheral tissues compared to those of the classical cardiovascular organs. It appeared, therefore, that the time was ripe for a meeting to consider a merger of interest in these two important but heretofore distinct areas of physiology.

Scientific advances over the past two decades have afforded unprecedented oppor­ tunities to understand the structure and function of receptors, receptor-ligand interactions, and receptor signaling. The extent ofprogress in this area is underscored by the recent Nobel Prize for Medicine and Physiology to Alfred Gilman and Martin Rodbell, both of whose work in understanding receptorlG-protein interactions has redefined the way in which we think of how hormones and neurochemicals exert their activity on cellular function. This book is replete with examples of current research approaches to help us better understand the cellular roles in which the renin-angiotensin system and the angiotensin receptors participate. Clearly, defining the structure of angiotensin receptor subtypes is an important first step in cJarifying the mechanisms by which these receptors take part in cellular function. However, the chapters within this book range far beyond structural studies and encompass research on tissue specific expression of the angiotensin receptor subtypes, the genetic regulation ofthese receptors, and the unique function ofvarious angiotensin subtypes in different organ systems, such as the brain, the reproductive system, adipose tissue, the heart, and the kidneys.

This book covers the entire spectrum of cardiovascular genomics. It is organized into three parts: Genes and Polymorphisms in Cardiovascular Disease; Gene Transfer for Cardiovascular Disease; and Regenerative Tissues for the Diseased Cardiovascular System. Leading clinical researchers provide an updated account of the most recent molecular approaches utilized to understand the cardiovascular system in both health and disease. It provides and excellent resource for students, researchers and clinicians on the potential of developing novel strategies for the control of cardiovascular disease.