Biochemistry Of Signal Transduction In Myocardium

The chapters in this volume are the Proceedings of the Satellite Symposium of the XVIth World Congress of the International Society for Heart Research on `Signal Transduction in Normal and Diseased Myocardium' which was held in Rotterdam at the Faculty of Medicine & Health Sciences of the Erasmus University, June 30 and July 1, 1995. Diverse and distinct auto-, para-, and endocrine stimuli arriving at the surface of endothelium, smooth muscle cells, cardiomyocytes and fibroblasts within the myocardium, engage cell type-specific receptors, which lead to transmission of signals across the cell plasma membrane and result in the production and activation of second messengers. The most common mechanism by which these second messengers function is via direct or indirect activation of specific protein kinases. The current challenge for scientists is to identify the specific substrates (e.g. metabolic enzymes, Ca2+-regulating proteins, transcription and mitotic factors) for the many protein kinases, to elucidate the biological significance of the cell type-specific expression heterogeneity of signalling proteins (e.g. membrane receptors, isoenzymes of protein kinase C, G-proteins) and to unravel the cross-talk interaction between the signalling systems (e.g. phospholipase C with adenylate cyclase and phospholipase C with phospholipase D). The multiplicity of receptor types, G-proteins, effector proteins, second messengers and protein kinases, their substrate proteins and the `cross-talk' interactions in the myocardium raises fundamental questions about the mechanisms that ensure the precision and timing of the myocardial responses to hormonal and pharmacological stimuli. This book provides an up-to-date source of information for all scientists and clinicians interested in the mechanisms by which external signals are transmitted to the interior and regulation of a variety of physiological, pathological and pharmacological responses.

Signal Transduction in Cardiovascular System Health and Disease highlights the major contributions of different signaling systems in modulating normal cardiovascular functions and how a perturbation in these signaling events leads to abnormal cell functions and cardiovascular disorders. This title is volume 3 in the new Springer series, Advances in Biochemistry in Health and Disease.

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.

Signal transduction pathways are at the core of most biological processes and are critical regulators of heart physiology and pathophysiology. The heart is both a transmitter and dynamic receptor of a variety of intracellular and extracellular stimuli, playing a critical role of an integrator of diverse signaling mechanisms. Alterations in signaling pathways are contributing factors in the development and progression of a broad spectrum of diseases, ranging from dysrhythmias and atherosclerosis to hypertension and the metabolic syndrome. Targeting specific components of these signaling pathways has been shown to be effective in preclinical studies with significant therapeutic impact. This book brings together current knowledge in cardiovascular cell signal transduction mechanisms, advances in novel therapeutic approaches to improve cardiac function, and discussion of future directions. Presented from a post-genomic perspective, this exciting book introduces important new ideas in cardiovascular systems biology. It is an invaluable reference for cardiology researchers and practitioners.

Despite the considerable success in treating diseases of the heart and blood vessels, they still remain the major cause of mortality throughout the world. One of the reasons underlying this problem is our lack of understanding of the molecular and cellular aspects of the processes involved. These problems are fully discussed in Cellular Interactions in Cardiac Pathophysiology, which draws together 25 contributions from leading investigators from all parts of the world. The contributions are grouped under three headings: Extracellular matrix and cardiocyte interaction; Myocytic adaptations and myocardial injury; and Signal transduction.

Signal Transduction in Cardiovascular System Health and Disease highlights the major contributions of different signaling systems in modulating normal cardiovascular functions and how a perturbation in these signaling events leads to abnormal cell functions and cardiovascular disorders. This title is volume 3 in the new Springer series, Advances in Biochemistry in Health and Disease.

This book presents a multidisciplinary approach to cardiac mechanotransduction. The chapters depict the many faces of the topic, from membrane and ion channel level to mechanics, biochemical signaling and regulation via hormone systems. Cardiac Mechanotransduction is of interest to basic life sciences, like physiology, biochemistry and pharmacology, but also to clinicians working with heart-related problems, such as cardiologists and internists.

A variety of metabolic processes are known to be intimately involved in the maintenance of cellular structure and function. It has also become clear that metabolic events involved in the synthesis and hydrolysis of ATP as well as for the synthesis of proteins and phospholipids are essential for cellular health. The regulation of cell function is generally achieved through participation of a wide variety of hormones and different signal transduction mechanisms for the activation/deactivation of some specific metabolic processes. In this regard cyclic AMP and calcium seem to play a crucial role. Various hormones are also known to affect the genetic machinery of all the cell; however, the exact signals for genetic control of cellular function are not well defined. In particular, the sequence of events concerned with remodelling of different types of cells under various pathological situations is poorly understood. In this book we have therefore dealt with some of these issues from biochemical, molecular biological, physiological, and pharmacological viewpoints. Special emphasis has been laid on understanding heart function and metabolism in health and disease in general, and cardiac hypertrophy, heart failure, and ischemic heart disease in particular. It is hoped that this multidisciplinary information will be of value to basic scientists and clinical investigators.