It is now well known that proteases are found everywhere, in viruses and bacteria as well as in all human, animal and plant cells, and play a role in a variety of biological functions ranging from digestion, fertilization, development to senescence and death. Under physiological conditions the ability of proteases is regulated by endogenous inhibitors. However, when the activity of proteases is not regulated appropriately, disease processes can result, as seen in Alzheimer s disease, cancer metastasis and tumor progression, inflammation and atherosclerosis. Thus it is evident that there is an absolute need for a tighter control of proteolytic activities in different cells and tissues.

Aimed at graduate students and researchers with an interest in cellular proteolytic events, "Role of Proteases in Cellular Dysfunctions" is the second book on Proteases in this series. The book consists of three parts in specified topics based on current literatures for a better understanding for the readers with respect to their subject-wise interests. The first section of this book covers a brief idea about the neuronal disorders and the involvement of proteases such as calpains, caspases and matrix metalloproteases (MMPs). The second section covers the deadly disease cancer and its relation to ubiquitin-proteasome system, MMPs and serine proteases. The last section is about the role of proteases such as calpains, MMPs and serine protease as well as urokinase type plasminogen activator receptor (uPAR) in causing cardiovascular defects. "

The biological membranes of cellular organization enfold an important group of membrane proteins called the ATPases, which are not only versatile in maintaining chemical gradient and electrical potential across the membrane but also bring metabolites necessary for cell metabolism and drive out toxins, waste products and solutes that otherwise can curb cell functions. ATPases are distributed virtually in all live forms starting from unicellular to multicellular and also in viruses. There are different types of ATPases, which differ in function and structure and in the type of ions they transport. The three main types of the ion pump ATPase family are: (i) P-type ATPases that transport different ions across membranes and Ca2+ATPases belongs to this catagory (ii) F-type ATPase in mitochondria, chloroplasts and bacterial plasma membranes produce ATP using the proton gradient; and (iii) V-type ATPase catalyzes ATP hydrolysis to transport solutes and maintains acidic pH in organelles like lysosomes. Genetic defects in either of the ATPases cause several diseases and a number of researches have demonstrated the involvement of the members of ATPases in the cell pathology and diseases, thereby penetrating exciting new areas of our understanding. In this book, the authors summarize recent knowledge about the molecular mechanisms associated with Ca2+-ATPase, V-ATPase and F-ATPase in intracellular and extracellular Ca2+ transport, mitochondrial ATP synthase, vesicular H+ transport, and lysosomal pH regulation. This book thereby bridges the gap between fundamental research and biomedical and pharmaceutical applications. The book provides an informative resource to improve ATPase research and modern therapeutic approaches toward different life threatening diseases that are associated with dysregulation of the ATPases.

Phospholipases generate lipid signaling molecules through their hydrolytic action on phospholipids and are known to regulate function of a variety of cells under normal and diseased conditions. While several physiological, biochemical and molecular techniques have identified key players involved in different disease processes, phospholipases have also emerged as critical players in the pathogenesis of a number of different diseases including cancer and heart disease. In addition, phospholipases are also implicated in such conditions as brain disorder/injury, kidney and immune cell dysfunction. Phospholipases in Health and Disease is a compilation of review articles dedicated to the study of the field with respect to biochemical and molecular mechanisms of normal and abnormal cell function. The wide range of area covered here is of interest to basic research scientists, clinicians and graduate students, who are engaged in studying pathophysiological basis of a variety of diseases. Furthermore, this book highlights the potential of the different phospholipases as therapeutic targets as well as part of prevention strategies. Twenty three articles in this book are organized in four sections that are designed to emphasize the most characterized forms of the phospholipases in mammalian cells. The first section discusses general aspect of phospholipases. Section two covers the role and function of phospholipase A in different pathophysiological conditions. The third section is focussed on phospholipase C which is believed to play a central role in transmembrane signaling. The final section covers phospholipase D which is present in a variety of different cells. The book illustrates that the activation of phospholipases is of fundamental importance in signal transduction affecting cell function. Overall, this book discusses the diverse mechanisms of phospholipase mediated signal transduction in different pathophysiological conditions and raises the possibility of specific forms of phospholipases serving as novel targets for drug development.

Na+-K+ ATPase or Na-pump ATPase, a member of "P"-type ATPase superfamily, is characterized by association of multiple isoforms mainly of it's - and - subunits. At present four different - ( -1, -2, -3 and -4) and three - ( -1, -2, and -3) isoforms have been identified in mammalian cells and their differential expressions are tissue specific. Regulation of Na+-K+ ATPase activity is an important but a complex process, which involves short-term and long-term mechanisms. Short-term regulation of Na+-K+ ATPase is either mediated by changes in intracellular Na+ concentrations that directly affect the Na+-pump activity or by phosphorylation/dephosphorylation-mediated by some stimulants leading to changes in its expression and transport properties. On the other hand, long-term regulation of Na+-K+ ATPase is mediated by hormones, such as mineralocorticoids and thyroid hormones, which cause changes in the transcription of genes of - and - subunits leading to an increased expression in the level of Na+-pump. Several studies have revealed a relatively new type of regulation that involves the association of small, single span membrane proteins with this enzyme. These proteins belong to the FXYD family, the members of which share a common signature sequence encompassing the transmembra ne domain adjacent to the isoform(s) of - subunits of Na+-K+ ATPase. Considering the extraordinary importance of Na+-K+ ATPase in cellular function, several internationally established investigators have contributed their articles in the monograph entitled "Regulation of Membrane Na+-K+ ATPase" for inspiring young scientists and graduate students to enrich their knowledge on the enzyme, and we are sure that this book will soon be considered as a comprehensive scientific literature in the area of Na+-K+ ATPase regulation in health and disease.

Current evidence suggests that the ischemic preconditioning response is a multi-factorial process consisting of an initial early trigger, an intermediate mediator, and an end effector. Each of these steps in is now its own intense area of investigation. The need to render the heart ischemic for a brief period to invoke the preconditioning response is currently the major factor limiting clinical application of this powerful cardioprotective strategy. Recent research efforts have utilized brief exposures to pharmacological agents, in lieu of a brief preconditioning ischemia, to trigger/mimic the ischemic preconditioning-induced response. The World Heart Congress held in Winnipeg in July 2001 provided a forum for the presentation of new insights into the basic mechanisms of ischemia and reperfusion injury, as well as novel strategies to protect the heart from cell death, ventricular arrhythmias, and contractile dysfunction. Many pioneers in the fields of ischemia-reperfusion injury and preconditioning-induced protection presented there and the chapters in this book represent selected papers from these symposia.

According to the World Health Report (2000 http:/ /www. who. int/whr), of the 55 million deaths worldwide in 1999, more than 16 million were secondary to car diovascular complications. With the prospect of world population increasing from the current level of 6 billion to 9 billion by the middle of this century, the burden of cardiac disease is going to increase astronomically. Furthermore, scientists are being challenged not only to reduce mortality, but also to improve quality of life. Thus, more than ever, intellectuals from different disciplines including biology, sociology, informatics and health care have to join forces to meet the mandate. The World Heart Congress with a focus on "Frontiers in Cardiovascular Health" held in Winnipeg during July 6-11, 2001, made a unique attempt to bring these specialists together to brainstorm and map out the course of action for cardiovascular research and health in the next century. Anytime there is a relative increase in the workload on the heart, there are adap tive myocardial as well as humoral responses. When these adaptations or remodel ing at the organ, subcellular or gene level, become inadequate for a proper tissue perfusion, the condition of heart failure ensues. Prevention of the factors leading to the relative increase in workload as well as a better understanding of the adap tive responses and their failure are some of the hopes to combat the morbidity and mortality due to heart failure.

Mechanisms of Heart Failure is based on papers selected from poster presentations made at the International Conference on Heart Failure, Winnipeg, May 20-23, 1994. Although the entire book is one continuous discussion of subcellular mechanisms of heart failure and its treatment, the presentation has been divided into three sections: the opening section on the subcellular basis of heart failure includes discussions of cytokines, signal transduction, metabolism, extracellular matrix, organ level changes and newer approaches to understanding the pathogenesis of heart failure. The second section focuses on the pathophysiological aspects of cardiomyopathies and their treatment. In the final section, medical, surgical and pharmacological approaches to the treatment of heart failure are discussed in clinical and animal laboratory settings.

This monograph contains 20 selected papers presented at the Symposium on Subcellular Basis of Contractile Failure which was held in Ottawa during May 11-13, 1989 and is designed for the benefit ofthose who were unable to attend this event. It is now increasingly becoming clear that an excessive amount of calcium is intimately involved in the pathogenesis of a wide variety of heart diseases. Accordingly, the investigations concerning the role of calcium chan nels and their regulatory mechanisms in heart function as well as of the intra cellular calcium overload in cardiac dysfunction are presented here. Since sodium is also considered to influence the cardiac contractile force by chang 2 ing the intracellular concentration of calcium through the Na +-Ca+ exchange 2 mechanism in the cell membrane, the role of Na +-Ca+ exchange in heart func tion as well as pathology of contractile failure is discussed. In view of the new ly discovered implications of the oxygen free radicals in cellular injury, papers concerning the role of these radicals in heart disease are included in this book. For the purpose of clarity, different chapters have been organized under three main headings: (I) Role of cations in heart function, (II) Cardiac hypertrophy and cardiomyopathies, and (III) Ischemic heart disease and cardiac failure."

Heart Hypertrophy and Failure brings together leading basic scientists and clinicians, presenting improved knowledge of the pathophysiology and treatment of the condition. The result is a synthesis of state-of-the-art information on molecular biology, cellular physiology and structure-function relationships in the cardiovascular system in health and disease. The papers presented describe fundamental mechanisms underlying changes in the cellular machinery during the development of cardiac hypertrophy and heart failure. Audience: Students, scientists, clinical and experimental cardiologists who seek to understand and manage the perplexing problems of hypertrophy and heart failure.

Pathophysiology of Heart Failure brings together leading basic scientists and clinicians, presenting new approaches to this complex problem, involving cardiomyopathic processes and ischemia perfusion injury. The result is a synthesis of state-of-the-art information on molecular biology, cellular physiology and structure-function relationships in the cardiovascular system. The role which excess intracellular calcium plays in the genesis of cardiac dysfunction is described as a fundamental mechanism underlying heart failure; one which may lead to improved prevention and treatment. Audience: Clinical and experimental cardiologists will find the book a helpful source of ideas and inspiration.

Proteases form one of the largest and most diverse families of enzymes known. Once considered primarily as "enzymes of digestion," it is now clear that proteases are involved in every aspect of cellular function. Members of the diverse families of proteases act to promote cellular proteolysis found in nature, and their deregulation may result in different pathophysiological conditions, such as tumor progression, vascular remodeling, atherosclerotic plaque progression, ulcer, rheumatoid arthritis, and Alzheimer's disease. Many micro-organisms require proteases for replication or use proteases as virulence factors, which have facilitated the development of protease-targeted therapies for a variety of parasitic diseases. Proteases in Health and Disease represents a comprehensive overview of the fascinating field of proteases by various renowned experts, and focuses on the recently elucidated functions of complex proteolytic systems in physiology and pathophysiology. Part A, Molecular and Biochemical Aspects of Proteases, illustrates some of the major proteases, such as calpains, matrix metalloproteases, fibrinolytic serine proteases, and aspartic proteases, which play a significant role in a variety of pathologies and may be a target for therapy either by their up regulation or down regulation. Part B, Involvement of Proteases in Diseases Processes, deals with the functional roles of the individual proteases in the progression of diseases such as cardiovascular and inflammatory lung disease, malaria, cholera, autism spectrum disorder, hepatitis, and ischemia-reperfusion injury induced cardiac diseases. With this multi-disciplinary scope, the book bridges the gap between fundamental research and biomedical and pharmaceutical applications, making this a thought-provoking reading for basic and applied scientists engaged in biomedical research.

Pathophysiology of Cardiovascular Disease has been divided into four sections that focus on heart dysfunction and its associated characteristics (hypertrophy, cardiomyopathy and failure); vascular dysfunction and disease; ischemic heart disease; and novel therapeutic interventions.
This volume is a compendium of different approaches to understanding cardiovascular disease and identifying the proteins, pathways and processes that impact it.

The Frontiers in Cardiovascular Health varies between and within nations, depend ing upon the level at which the battle is fought for better cardiovascular health. According to the 1997 World Health Report, 15 million deaths (i. e. 30% of the total number of deaths) were attributable to cardiovascular diseases and this number is on the rise. The projection for the year 2020 is quite alarming with an expected cardiovascular mortality reaching 50 million. Much of this burden is projected to occur in developing countries, more specifically in the most populous countries of the world, namely China and India. These countries are already burdened with infectious and parasitic diseases and are trying to eradicate such diseases. With increasing life expectancies people all over the world, especially in developing coun tries, are exposed to degenerative atherosclerosis resulting in increased cardiovascu lar mortality and morbidity. In developing countries, resources available for health care are very limited. For example many of the African countries spend less than $10 per person per year on his/her entire health care let alone cardiovascular health. The average health care budget for nearly two thirds of the global population is well below $100 per year, on a per capita basis. Therefore, in developing countries health promotion and primary prevention are the frontiers by necessity. Improving awareness and health education is not only a matter of choice but is an absolute necessity.

In 1982, as chance would have it again, an opportunity appeared to Jom the Department of Physiology at Kuwait University. P. Braveny spend four years there, teaching, doing some research, recovering former international contacts. Coming back home, he faced the same gloomy, motionless disfavor as before. November 1989 turned P. Bravenfs career upside down. Immediately after the fall ofthe communist regime, he was elected vice-dean and later dean ofthe Faculty of Medicine, promoted full professor in physiology and appointed the head of the Department ofPhysiology. From 1992 to 1998 P. Braveny served as the vice-rector of Masaryk University. His professional career culminated in his presidency of the XIV World Congress of ISHR in Prague. Understandably, in the following years, he become interested (in his tutor's footsteps) in history of physiology and pub- lished two monoghaphs (E. Babak andV Kruta). This CV would be an incomplete one without mentioning his broad interests in natural sciences and in art, particu- larly music and painting. As a tutored amateur he has acquired certain success in the latter. When reviewing P. Bravenfs whole-life work, largely done under adverse cir- cumstances with minimum financial support, his almost two hundred papers, innu- merable essays and four monographs are a commensurate result. In appreciation, he was awarded honorary membership of the Czech Medical Society, Physiological Society and Cardiological Society, Gold Medal of Masaryk University, Ministry of Education Award etc. Bohuslav Ostadal Makoto Nagano Naranjan S.

The heart has a very high energy demand but very little energy reserves. In order to sustain contractile function, the heart has to continually produce a large amount of ATP.The heart utilizes free fatty acids mainly and carbohydrates to some extent as substrates for making energy and any change in this energy supply can seriously compromise cardiac function.It has emerged that alterations in cardiac energy metabolism are a major contributor to the development of a number of different forms of heart disease.It is also now known that optimizing energy metabolism in the heart is a viable and important approach to treating various forms of heart disease.

"Cardiac Energy Metabolism in Health and Disease" describes the research advances that have been made in understanding what controls cardiac energy metabolism at molecular, transcriptional and physiological levels.It also describes how alterations in energy metabolism contribute to the development of heart dysfunction and how optimization of energy metabolism can be used to treat heart disease.The topics covered include a discussion of the effects of myocardial ischemia, diabetes, obesity, hypertrophy, heart failure, and genetic disorders of mitochondrial oxidative metabolism on cardiac energetics.The treatment of heart disease by optimizing energy metabolism is also discussed, which includes increasing overall energy production as well as increasing the efficiency of energy production and switching energy substrate preference of the heart. This book will be a valuable source of information to graduate students, postdoctoral fellows, and investigators in the field of experimental cardiology as well as biochemists, physiologists, pharmacologists, cardiologists, cardiovascular surgeons and other health professionals."

Research at the molecular and the cellular level has greatly enhanced our understanding of the pathogenesis and management of heart disease. Valuable contributions, towards this end, have been made by scientists from different dis ciplines including biochemistry, physiology, pathology, molecular biology and biophysics. We felt that it would be of interest and value to bring together ex perts from diverse specialities to present their work and to discuss the common problems encountered in their endeavours. In accordance, a symposium was organised in February 1988 at the Postgraduate Institute of Medical Education & Research, Chandigarh. It was held during the annual meeting of the Indian section of the International Society for Heart Research. This book is a compila tion of some of the papers presented at the symposium. The symposium was sponsored by the Council on Cardiac Metabolism of the International Society and Federation of Cardiology. A number of Indian or ganisations gave generous financial help. These included the National Academy of Medical Sciences, Indian Council of Medical Research, Council of Scientific and Industrial Research and Department of Science and Technology. Desktop publishing was used to prepare this volume. In doing so we came to appreciate the remarkable qualities, skills and help rendered by Professor Dharam Vir. For typing the manuscripts and for other secretarial assistance we gratefully acknowledge the help of Ravinder and Sawtantar. PATHOPHYSIOLOGY AND PHARMACOLOGY OF HEART DISEASE 1 THE NEWBORN PIG HEART, A SUPERIOR ANIMAL MODEL OF CARDIAC HYPERTROPHY Howard E."

The importance of heart and artery disease as a cause of death and disability is difficult to exaggerate: it causes over half of all deaths in the western world and now accounts for one-quarter of deaths in the entire world. This appalling incidence persists in spite of commendable progress in treatment and prevention, particularly in the last two or three decades. Deaths from coronary disease have decreased by a third in the past twenty years and stroke has decreased by a half in the same period. This remarkable improvement, saving thousands of lives per year, has come about due to changes in life style (low fat diet, control of high blood pressure, less smoking and more exercise) and progress in treatment (more effective drugs, coronary care units, pacemakers, and cardiac surgery). Progress in understanding the pathophysiologic and pharn, acologic mechanisms operative in heart disease have been paramount in the development of more rational and more effective therapy. Dramatic and spectacular surgical treatments have fired the public imagination. Bypass surgery is commonplace and results in complete or considerable relief of symptoms in the majority of patients operated upon

Molecular Defects in Cardiovascular Diseaseprovides an in-depth discussion of the molecular mechanisms underlying the genesis of cardiovascular defects and the implications this has on current and emerging targeted therapeutics. Divided into three sections, this book covers the scientific foundations of our present understanding as well as the array of clinical manifestations and their treatment. The first section covers Molecular Mechanisms of Heart Disease, with discussion of the development of cardiovascular dysfunction. The remaining two sections provide a more clinical focus. The second, Cardiac Hypertrophy and Heart Failure deals with metabolic derangements, Ca2+ handling, and subcellular remodeling. It illustrates the wide variety of molecular defects which may serve as targets associated with the transition from cardiac hypertrophy to advanced heart failure. The third section, Hypertension and Diabetes, provides molecular rationale for the pathogenesis of hypertension and diabetic cardiomyopathy, as well as highlighting the importance of hormones toward this end.

A necessary resource for clinicians and researchers, this book elucidates the experimental basis of the practice of cardiology. It is the culmination of our advances in the understanding of cardiovascular molecular biology and a blueprint for the efficacious use of targeted therapies.

In the course of the last two decades, it has become increasingly evident that the sarcolemmal, sarcoplasmic reticular and mitochondrial membrane systems play an important role in determining the status of heart funotion in health and disease. These organelles have been shown to be intimately involved in the regulation of cation movements during the contraotion-relaxation cycle. Various proteins imbedded in the phospholipid 2+ + - + + bilayers of these membranes control Ca, Na, Cl, K and H concentrations within the oytoplasm by indirect or direct means. Cationic channels, Na+, + 2+ 2+ 2+ + 2+ + + K -ATPase, Ca IMg ATPase, Ca pump, Na -Ca exchanger, Na -II exchanger and adenylate cyclase affect myocardial funotion and viability through their role as regulators of specific ion movements. However, proteins are not the only important constituents of the membrane. Any disturbance in the interaction between proteins and phospholipids in the membrane has been suggested to alter the funotion of the organelles, upset ionic homeostasis and precipitate the development of abnormalities in oardiac performance. It is, therefore, orucial to understand the faotors whioh regulate membrane funotion in their totality if we are to oomprehend the nature of heart performanoe in healthy subjects. Similarly, the study of membrane dysfunotion in a wide variety of experimental models of heart disease at various stages of failure is essential if we are to fully understand the pathogenesis of heart dysfunotion and improve its treatment.

It is indeed ironical that in the absence of a complete knowledge of Pathophysiology, clinical cardiologists are left with no choice but to do the best they can to help the patient with the armamentarium of drugs at their disposal. But nothing could be further from truth than to treat the diagnosed end point of a disease process without a full understanding of its patho physiology. This point was eloquently made by Dr. Arnold Katz in his Presidential Address (Chapter 1) at the 8th Annual Meeting of the American Section of the International Society for Heart Research held in Winnipeg, Canada, July 8-11, 1986. This volume represents a part of the scientific proceedings of this Meeting. From a reading of this treatise it will become evident that discoveries of newer scientific facts as well as a better understanding of pathophysiology are continuously influencing/ improving our therapeutic approaches in modern medicine. In this book, latest biochemical, physiological and pharmacological findings on different experimental models such as Myocaridal hypertrophy, Hypertension and heart failure, Diabetes, Cardio myopathies and Cardiac function in shock are described by internationally recognised experts. Hopefully information presented here will provide another building block to the edifice of Science of Cardiology which we all are trying to create. Acknowledgements We are grateful to the following Agencies and Foundations for their generous financial support of the Symposium, which formed the basis of this book. A. Major Contributors: 1. Manitoba Heart Foundation 2. Sterling-Winthrop Research Institute 3. Squibb Canada, Inc."

The relationship between angiotensin II and hypertension was established in 1898 when angiotensin II was shown to modulate systemic blood pressure. Over the intervening decades, a complete characterization of the renin-angiotensin system (RAS) has been achieved, and our understanding of its biochemistry and physiology has led to the directed development of agents such as ACE inhibitors and receptor antagonists capable of controlling hypertension. More recently, it was shown that angiotensin II is secreted within certain tissues, and that these tissue-specific systems operate independently of the systemic RAS. The novel concept that angiotensin II regulates a number of cardiovascular processes that are unrelated to blood pressure has renewed the interest of both basic and clinical scientists in angiotensin II. The association between angiotensin II and cardiac growth, in particular, has indicated that therapies currently in use for hypertension may have direct application to the treatment of heart failure. Angiotensin II Receptor Blockade: Physiological and Clinical Implications focuses on the most recent developments in the molecular biology, cellular physiology and structure-function relationships of angiotensin II and its receptors. In addition, this volume covers the current therapeutic uses for angiotensin receptor antagonists and considers their potential future applications. This volume will be a valuable resource for scientists, practising clinicians and students who are attempting to extend their knowledge in the field of hypertension and heart failure, and who are devoted to improving cardiovascular health.

In an attempt to clarify the situation regarding the diagnosis, pathogenesis and therapeutics of cardiovascular dysfunction in diabetes, an International Symposium on Diabetic Heart was held in Tokyo, Japan during October, 1989. Thirty-two selected articles from the poster presentations, compiled in this book, have been grouped in four sections, namely (a) Evaluation of Cardiovascular Problems, (b) Interactions of Diabetes and Hypertension, (c) Pathophysiological Aspects of Cardiovascular Dysfunction in Diabetes, and (d) Pharmacological and Therapeutic Aspects of Diabetic Heart. It is hoped that the contents of these chapters will provide adequate information regarding the current status of cardiovascular abnormalities in diabetes and this book will be of great interest to both clinical and experimental cardiologists as well as endocrinologists interested in diabetes.

As the majority of cardiovascular deaths are related to myocardial ischemia, it is necessary to understand the various aspects of ischemic heart disease. In this regard, it is noteworthy that ischemic heart disease is commonly associated with atherosclerosis, coronary spasm, as well as thrombosis leading to the development of arrhythmias, cardiovascular cell damage, myocardial infarction, cardiac hypertrophy and congestive heart failure. Furthermore, it is also important to appreciate various physiological, electrophysiological and biochemical processes in the normal heart if we are to understand their significance under pathological situations. Heart Function in Health and Disease has been organized in five sections to provide an outline of a complex problem in a convenient manner. One section of this book is devoted to shedding light on the restructuring and ontogenic changes in the developing heart whereas in the next section some hypertrophic alterations due to chronic hypoxia are described. The third and fourth sections of this book are concerned with the regulation of cardiac channels as well as signal transduction mechanisms and cardiac electric field. The fifth section contains some pathophysiological events during the development of cardiac hypertrophy and heart failure. All of these areas encompass a significant body of new information that will be invaluable to those who work in the field of cardiovascular sciences, as well as those who treat people with heart disease.

Whenever the heart is challenged with an increased work load for a prolonged period, it responds by increasing its muscle mass--a phenomenon known as cardiac hypertrophy. Although cardiac hypertrophy is commonly seen under physiological conditions such as development and exercise, a wide variety of pathological situa tions such as hypertension (pressure overload), valvular defects (volume overload), myocardial infarction (muscle loss), and cardiomyopathy (muscle disease) are also known to result in cardiac hypertrophy. Various hormones such as catecholamines, thyroid hormones, angiotensin II, endothelin, and growth factors have also been shown to induce cardiac hypertrophy. Although the exact mechanisms underlying or pathological forrns of cardiac hypertrophy are poorly under the physiological stood, an increase in the intraventricular pressure is believed to represent the major stimulus for the development of cardiac hypertrophy. In this regard, stretching of the cardiac muscle has been shown to induce the hypertrophic response, but the role of metabolic influences in this process cannot be ruled out. Furthermore, different hormones and other interventions in the absence of stretch have been observed to stimulate protein synthesis in both isolated cardiomyocyte and vascular myocyte preparations. Nonetheless, it is becoming dear that receptor as well as phospholipid linked signal transduction pathways are activated in some specific manner depend ing upon the initial hypertrophic stimulus, and these then result in an increase in the size and mass of cardiomyocytes.

This book covers the latest developments in the therapeutic implications of angiogenesis, ranging from angiogenesis in the brain, angiogenesis in cancer, angiogenesis' role in atherosclerosis and heart disease as well as metabolic disorders and peripheral vascular disease. The book is comprehensive in its coverage of angiogenesis in a diverse set of diseases and examines the role of cellular and subcellular structures during the development of angiogenesis. Well-organized and thorough, this is an ideal book for researchers and biomedical engineers working in the field of therapeutic implications of angiogenesis. This book also: Covers the basics of the physiology of angiogenesis, including VEGF pathways in angiogenesis, integr ins in angiogenesis, angiogenesis and exercise physiology, and more Details the role of angiogenesis in atherosclerosis and heart disease, including vascular endothelial growth factor and atherosclerotic plaque progression as well as angiogenesis and heart failure Illustrates in detail brain angiogenesis after stroke and the relationship between angiogenesis and Alzheimer's disease