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.

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.

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

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.

Diabetes has long been recognized as a disease of high blood sugar, and there has been a continuous search of the exact reason for its development and effective treatment. In 2005, the World Health Organization had estimated that more than 180 million people worldwide suffer from diabetes mellitus and indicated that this figure is likely to double within the next 20 years. Among the 3.8 million deaths each year associated with diabetes, about two thirds are attributable to cardiovascular complications, and diabetes is now considered to be a major metabolic risk factor for the occurrence of heart disease. Diabetic Cardiomyopathy: Biochemical and Molecular Mechanisms is a compilation of review articles devoted to the study on the topic with respect to biochemical and molecular mechanisms of hyperglycaemia. The wide range of areas covered here is of interest to basic research scientists, clinicians and graduate students, who are devoted to study the pathogenesis of diabetes-induced cardiovascular dysfunction. Furthermore, some chapters are directed towards increasing our understanding of novel ways for the prevention/treatment of cardiomyopathy. Twenty five articles in this book are organized in three sections. The first section discusses general aspects of the metabolic derangements in diabetic cardiomyopathy including metabolic alterations and substrate utilization as well as cardiac remodelling in the heart; role of diet in the development of metabolic syndrome in the heart; effect of hyperglycaemia in terms of biochemical and structural alterations in heart. In the second section, several cellular and molecular mechanisms are discussed indicating that diabetic cardiomyopathy is a multifactorial and complex problem. The third section discusses the prevention and treatment of diabetes using appropriate diet, proper supplements including antioxidants, angiotensin inhibitors and some other drugs. All in all, this book discusses the diverse mechanisms of diabetic cardiomyopathy with some information on new therapeutic approaches for finding solutions to prevent or reverse the development of cardiac dysfunction.

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.

In view of rapidly growing research in the deregulation of proteases and their impact in human health and diseases, this book will highlight existing and emerging research in this exciting area. In-depth critical state-of-the-art reviews will be written by established investigators on proteases dysfunctions associated with pathogenesis of different diseases that are known to occur due to deregulation of proteolytic systems. Multidisciplinary approaches demonstrating biochemical and signal transduction mechanisms associated with deregulation of proteases leading to manifestation of the diseases will be discussed. The book highlights the roles of both intracellular and extracellular proteases in health and disease.

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.

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.

This book summarizes present knowledge of different mechanisms involved in the development of positive and negative consequences of cardiac adaptation. Particular attention is paid to the still underestimated adaptive cardiac responses during development, to adaptation to the frequently occurring pressure and volume overload as well as to cardiac changes, induced by enduring exercise and chronic hypoxia. Cardiac Adaptations will be of great value to cardiovascular investigators, who will find this book highly useful in their cardiovascular studies for finding solutions in diverse pathological conditions; it will also appeal to students, fellows, scientists, and clinicians interested in cardiovascular abnormalities.

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."

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.

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.

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. "

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 coronary flow is inadequate to provide enough oxygen to meet the energy demands of the tissue, the heart becomes ischemic. Manifestations of myocardial ischemia include depression in contractile activity, changes in metabolic pattern, abnormalities in ultrastructure, and alterations in membrane potential. Ischemic changes during the early phase are reversible but as the period of ischemia is extended, the injury becomes irreversible. The transition from reversible to irreversible ischemic injury is usually associated with some membrane defects. It is worthwhile to consider that the irreversible damage to the ischemic myocardium occurs when the sarcolemmal membrane is altered in suoh a way that it would promote 2 a net gain of ca + in the cardiac cell upon reinstitution of blood flow. Suoh a lesion could result when mechanisms for the entry as well as removal 2 of ca + from the myocardial oell become defective. In this regard, 2 depression of the sarcolemmal ca + pump would favour the oocurrenoe of 2 intracellular ca + overload. Furthermore, inhibition of the Na+-K+ pump would lead to elevation of myoplasmic Na+ which oould then increase the 2 2 intracellular concentration of ca + through the sarcolemmal Na+-ca + exchange mechanism. In faot recent studies have revealed an inhibition of 2 the sarcolemmal Na+-ca + exchange mechanism in the ischemic heart and this 2 change could also contribute towards the occurrence of intracellular ca + 2 overload.

Diabetes and cardiovascular disease together account for the largest portion of health care spending compared to all other diseases in Western society. This work seeks to provide an understanding of the causes of diabetes and its cardiovascular complications. As this understanding becomes more widely appreciated, it will serve as a foundation for evidence-based care and wider acceptance of sound science. The International Conference on Diabetes and Cardiovascular Disease, held in Winnipeg, in June 1999, was organized to bring together a multi-disciplinary group of researchers dedicated to further knowledge amongst researchers, care givers, and the managers of the health system. The invited speakers submitted their works for publication, which serves as the basis for this book. Major themes include: epidemiology of diabetes mellitus, metabolic risk factors in diabetes and cardiovascular disease, hypertension in diabetes mellitus, cardiac function in diabetes, glycemic control and improved cardiovascular function, diabetes management, and endothelial function in diabetes.

Cellular signaling in cardiac muscle refers to the myriad of stimuli and responses that direct and control the physiological operation of this organ. Our understand ing of these complex signaling cascades has increased dramatically over the past few decades with the advent of molecular tools for their dissection. Moreover, this infor mation is beginning to provide tangible targets towards manipulating cardiac func tion in the setting of cardiovascular disease. The mechanisms and factors that regulate cardiac cell growth are of particular interest as both adaptive and maladaptive responses can occur during cardiac hypertrophy. Cardiac hypertrophy describes the increase in individual cardiac myocyte size that is accomplished through the series and/or parallel addition of sarcomeres. The ability of cardiac muscle to increase in size through hyperplasia becomes highly restricted or negligible shortly after birth. Consequently, the increase in heart size associated with development and growth of an individual occurs through hypertrophy. In response to a chronic increase in workload, cardiac muscle cells can dramatically increase in size to face their increasing contractile demands. While this plasticity is clearly a ben eficial response under many conditions, it can be highly deleterious and inappropri ate under others. For example, cardiac hypertrophy associated with endurance exercise clearly enhances athletic performance. In contrast, the hypertrophy associated with chronic hypertension, stenotic or regurgitant heart valves, or following a myocardial infarction often continues far beyond the period where this adaptive response is ben eficial.

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.

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 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.

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.

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.

Thistext, as the tide states, is acompilationofpapersdevoted to the studyofath- erosclerosis,hypertensionanddiabetes.Thesethree distinctdisease entities,although not entirely unrelated, are three ofthe most important disease conditions in the world today.As such, this volumeofresearch papers isofobvious medical impor- tance.Thejustificationofthe energy,time and financial resources directed towards the studyofeachofthese three diseases requiressome discussion. The majority of papers amongst the three diseases that are discussed in this volume are dedicated to the studyofatherosclerosis.This is not by accident.Car- diovasculardisease isthenumberonekillertodayintheworld. IntheUnitedStates almost61 millionAmericanshaveoneormoreformsofcardiovasculardisease.These diseases claimed nearly 1million lives in 1998 alone.Although approximately 80% ofthosewho dieofcardiovasculardisease are 65 yearsofageorolder,asignificant numberofpeople are killed by cardiovascular disease below the ageof65.Ather- osclerotic heart disease in the eoronary vaseulature eausedapproximately~ million deaths in the United States in 1998.At least 12,400,000people are alive todayin the United States with a historyofmyocardial infarctions or ehest pain or both. Clearly,atherosclerotie disease inthe heart isamajormedicalproblem.This disease affeetsbothmenandwomen.Althoughmen are more likelyto experienee aheart attaekand are atgreater risk for eardiovaseular disease,more then ~ofthe people alive today with a historyofheart attacks or angina are females. As weIl,women whodo havemyoeardialinfarctionsare twice aslikely to diefromtheeventwithin afew weeks.Atheroscleroticvasculardisease isnotlimitedtojustthe heart.Anath- erosclerotic ischemic event is the primary causeofstroke today.Although it isnot weIl appreciated, stroke is the number 3 killer inAmerica today and the leading causeofdebilitatingneurological damage.Atherosclerotic vascular disease therefore, has acostintermsofhuman life,qualityoflifeandfinancialburden today thatno otherdisease canmatch.Theseriousnessofthis medicalproblemdemands research attention.

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.