Download or read book Signal Transduction Mechanisms Regulating Cardiac Myocyte Hypertrophy and Gene Expression written by Wirt Anderson Hines and published by . This book was released on 1999 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Signal Transduction and Cardiac Hypertrophy written by Naranjan S. Dhalla and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 778 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Signaling in the Heart written by José Marín-García and published by Springer Science & Business Media. This book was released on 2011-06-21 with total page 511 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Signal Transduction Mechanisms and Nuclear Effectors in Gene Expression During Hypertrophy of Cardiac Myocytes written by Sampsa Pikkarainen and published by . This book was released on 2003 with total page 100 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Regulation of Myocardial Growth and Apoptosis by Stress Kinase Signal Transduction Pathways in Neonatal Cardiac Myocytes written by Dietmar K. Zechner and published by . This book was released on 1998 with total page 516 pages. Available in PDF, EPUB and Kindle. Book excerpt: During the clinical pathology of cardiac hypertrophy, the expression pattern of genes and morphological features of ventricular myocytes change. As cardiac myocytes re-express embryonic genes such as the hormone, atrial natriuretic factor, or $\alpha$-skeletal actin their cell size increases and sarcomeric organization is induced. At the late stage of cardiac hypertrophy, apoptosis can be observed contributing to the deterioration of the heart. Utilizing neonatal ventricular myocytes as a model system, the potential involvement of the JNK and p38 stress kinase signal transduction pathways in the induction of hypertrophic features and apoptosis was tested. To specifically activate or inhibit JNK or p38 signaling, plasmids expressing constitutively-active or dominant-negative kinases, known to be part of either pathway, were transfected into ventricular myocytes. Moreover the SB 203580 compound was utilized to inhibit p38 specifically. Activation of the p38 signal transduction pathway by cotransfection of MKK6 or stimulation by phenylephrine induces atrial natriuretic factor, as well as alpha-skeletal actin, promoter activity, and increases cell size and sarcomeric organization, while inhibiting apoptosis. JNK signaling, can cooperate with p38 signaling pathways in the induction of atrial natriuretic factor promoter activity. However, constitutively active MEKK1, which can activate ERK, JNK and p38 in cardiac myocytes, can also induce apoptosis in ventricular myocytes. This study suggests the involvement of stress kinase signal transduction pathways in the regulation of hypertrophy and apoptosis in neonatal ventricular myocytes.

Download or read book Biochemistry of Signal Transduction in Myocardium written by Jos M.J. Lamers and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 263 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Cardiac Mechanotransduction written by Matti Weckström and published by Springer Science & Business Media. This book was released on 2007-12-22 with total page 158 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Signal Transduction in the Cardiovascular System in Health and Disease written by Ashok K. Srivastava and published by Springer Science & Business Media. This book was released on 2008-09-20 with total page 426 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Mechanoresponsive Mechanisms In Hypertrophic Cardiac Remodeling written by Todd Haswell Kimball and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: All cells of the body are under some form of mechanical load and these forces are part of the factors defining cell type specificity. The mechanical environment influences cellular behavior and is the basis of mechanobiology. The forces acting on cells must be met with a cellular response, as the input signals are transduced to molecular mechanisms that drive gene regulation. In the heart, the distinct roles of cardiomyocytes and fibroblasts, as fibroblasts enforce tissue stiffness homeostasis through extracellular matrix maintenance and cardiomyocyte contraction-relaxation cycles work against this stiffness with every heartbeat, enable each to respond to cardiac stressors through differential gene expression, changing their cellular physical phenotype. At the cellular level, cardiac hypertrophy is a growth of the cardiomyocyte (without proliferation) and increased interstitial fibrosis, and these phenotypes are the result of changes to gene expression. While the gene expression program induced by cardiac hypertrophy is well documented, this dissertation unravels mechanosensitive mechanisms activated by changes to the myocardial environment and cellular forces driving dysfunctional gene regulation perpetuating cardiac disease. Gene translation ends in the nucleus; however, it does not always start there. We viewed gene expression as an end point, being influenced by a number of factors outside the nucleus, including metabolism, nucleoskeletal, cytoskeletal, sarcomere organization, sarcolemmal signal transduction pathways, and the tissue environment. In examining transcriptional influence outside the nucleus, we first summarize the bidirectional effect of metabolic and gene regulation dysfunction in heart disease, as metabolic substrates and intermediates impact cardiac epigenetics and chromatin stores information. We report our findings from our pressure overload induced cardiac hypertrophy studies, demonstrating cardiomyocyte cellular remodeling influences nucleoskeletal ultrastructure through the expression of the structural and chromatin binding protein Lamin A/C. We phenotypically characterize an [alpha]1-adrenergic model of cardiac hypertrophy and investigate cell specific mechanism driving tissue remodeling and cellular mechanosensitive pathways underlying pathological stress. Through these studies, we explore the cardiac stressors that remodel the heart tissue during hypertrophy and the cellular mechanisms altering the cellular phenotype through gene regulation.

Download or read book The Hypertrophied Heart written by Nobuakira Takeda and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 490 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Cardiac Hypertrophy and Failure written by Bernard Swynghedauw and published by . This book was released on 1990 with total page 718 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiac insufficiency, a major cause of premature mortality, is a key focus of medical and pharmaceutical research. This book aims to bring clinicians and researchers up-to-date on recent biophysical, cellular physiological and molecular biological developments and their clinical applications.

Download or read book Cardiac Regeneration written by Masaki Ieda and published by Springer. This book was released on 2017-10-27 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Volume of the series Cardiac and Vascular Biology offers a comprehensive and exciting, state-of-the-art work on the current options and potentials of cardiac regeneration and repair. Several techniques and approaches have been developed for heart failure repair: direct injection of cells, programming of scar tissue into functional myocardium, and tissue-engineered heart muscle support. The book introduces the rationale for these different approaches in cell-based heart regeneration and discusses the most important considerations for clinical translation. Expert authors discuss when, why, and how heart muscle can be salvaged. The book represents a valuable resource for stem cell researchers, cardiologists, bioengineers, and biomedical scientists studying cardiac function and regeneration.

Download or read book Systems Analysis of Mechano Sensitive Signaling Networks Regulating Gene Expression in Cardiomyocytes and Adventitial Fibroblasts written by Shulin Cao and published by . This book was released on 2021 with total page 207 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cells such as myocytes and adventitial fibroblasts are responsive to mechanical cues in their local environment. In response to mechanical loads, a variety of mechano-transduction mechanisms and signaling pathways are activated to regulate their response to the altered conditions. In order to define mechano-signaling networks and their role in cellular function and remodeling, we have adapted and refined previously published systems models of myocyte hypertrophy. Using uncertainty quantification, we first found that the model accuracy was robust to parameter changes over a wide range with model outputs being least sensitive to time constants and most affected by uncertainty in reaction weights. We also found epistemic uncertainty in the reaction logic of the model could greatly affect model accuracy while uncertainty in the validation data had a modest effect on model accuracy. As a step forward toward understanding myocyte response to external loading, including direction-dependent pathways, we extended this previous network model to include the transcriptional regulatory networks controlling gene expression as well as protein translation, and introduce a mass-action method to model quantitative gene expression. By incorporating RNA-sequencing data, this new approach displayed high accuracy with 69% agreement overall and 72% agreement for predicted differentially expressed genes in response to longitudinal stretch. We further found that the difference between transverse and longitudinal stretch responses in cardiomyocytes could be related to the sensitivity of directional mechanotransduction, with the sensitivity of longitudinal stretch being greater than transverse. Upon analyzing genes regulated by multiple TFs, we found that expression of these genes didn't monotonically change with the number of TFs, which indicates TF regulation effects may saturate faster when multiple TFs coregulate gene expression. Moreover, we identified AT1 and ET1 receptors as main regulators of the stretch induced responses through receptor inhibition simulations and subsequent experiments. A similar approach was used to study mechanical signaling and remodeling responses in PAAFs. In the current work, we have modified an existing systems model of cardiac fibroblast signaling to PAAFs and the cellular regulation of profibrotic signaling by combining both in-vitro and in-silico models of cell signaling in response to altered mechanical conditions. A UQ analysis on this model highlighted parameters to be optimized and network modules to be elucidated with more experiments. The signaling model in PAAFs and the subsequent experiments identified that both stretch and increased substrate stiffness regulated profibrotic genes, while no interaction effect was found between stretch and stiffness for several key genes studied. In addition, the activation of fibronectin expression by stretch in PAAFs may be angiotensin-independent when the cells are adhered on stiff but not soft substrates. While these signaling network models can help distinguish regulators and their sensitivity to different mechanical stimuli, it is not known how these regulators participate in gene regulation of in-vivo hypertrophy. In the future, these signaling network models can be used to identify key regulators of hypertrophy-related heart failure and tissue fibrosis and provide support for drug discovery.

Download or read book Transcriptional Regulation of Cardiac Hypertrophy and Heart Failure written by and published by . This book was released on 2006 with total page 241 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiac hypertrophy and dilatation are mediated by neuro-endocrine factors, internal stretch and stress sensitive signaling pathways, which in turn transduce alterations in cardiac gene expression through specific transcription factors. This dissertation will, in the first section, provide direct evidence for transcription factor myocyte enhancer factor 2 (MEF2) in the regulation of cardiac dilation and fibrosis through reprogramming cardiac gene expression; in the second section, introduce a novel secreted factor growth differentiation factor 15 (GDF15) as a cardiac anti-hypertrophic and protective factor. The MEF2 family of transcription factors have been indirectly implicated as a downstream mediator of hypertrophic signaling pathways. In this dissertation, we demonstrate directly that MEF2 induce dilated cardiomyopathy and the lengthening of myocytes without a primary induction of cardiac hypertrophy. Cardiac-specific overexpression of MEF2A or MEF2C showed spontaneous cardiomyopathy, which was not altered by activated calcineurin, or developed more fulminant disease following pressure overload. In cultured cardiomyocytes, MEF2A and MEF2C overexpression induced sarcomeric disorganization and focal elongation. Mechanistically, MEF2A and MEF2C programmed similar alteration in gene expression that included extracellular matrix remodeling, ion handling, and metabolic genes. Indeed, cultured cardiomyocytes overexpressing MEF2A, or adult myocytes from MEF2A transgenic hearts, showed reduced transient outward currents, suggesting a proximal mechanism underlying MEF2-dependent cardiomyopathy. During the analysis of gene reprogramming by MEF2, we noted dramatic induction of GDF15. GDF15 is induced by conditions that promote hypertrophy and dilation. Transgenic mice with cardiac-specific overexpression of GDF15 were normal, but were partially resistant to induced hypertrophy. GDF15 antagonized induced hypertrophy in cultured cardiomyocyte. Transient expression of GDF15 by intravenous adenoviral delivery, or by direct injection of recombinant protein, attenuated ventricular dilation and heart failure in MLP null mice through an endocrine effect. Conversely, Gdf15 null mice showed enhanced cardiac hypertrophic growth, and a pronounced loss in ventricular performance following stimulation. Mechanistically, GDF15 promoted activation of Smad2/3, which was partially responsible for the anti-hypertrophic effects. These results identify GDF15 as a novel endocrine factor that antagonizes the hypertrophic response and loss of ventricular performance.

Download or read book Dilated Cardiomyopathy written by Gianfranco Sinagra and published by Springer. This book was released on 2019-05-17 with total page 241 pages. Available in PDF, EPUB and Kindle. Book excerpt: This open access book presents a comprehensive overview of dilated cardiomyopathy, providing readers with practical guidelines for its clinical management. The first part of the book analyzes in detail the disease’s pathophysiology, its diagnostic work up as well as the prognostic stratification, and illustrates the role of genetics and gene-environment interaction. The second part presents current and future treatment options, highlighting the importance of long-term and individualized treatments and follow-up. Furthermore, it discusses open issues, such as the apparent healing phenomenon, the early prognosis of arrhythmic events or the use of genetic testing in clinical practice. Offering a multidisciplinary approach for optimizing the clinical management of DCM, this book is an invaluable aid not only for the clinical cardiologists, but for all physicians involved in the care of this challenging disease.

Download or read book Stress Activated Protein Kinases written by Francesc Posas and published by Springer Science & Business Media. This book was released on 2008-01-24 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book leading researchers in the field discuss the state-of-the-art of many aspects of SAPK signaling in various systems from yeast to mammals. These include various chapters on regulatory mechanisms as well as the contribution of the SAPK signaling pathways to processes such as gene expression, metabolism, cell cycle regulation, immune responses and tumorigenesis. Written by international experts, the book will appeal to cell biologists and biochemists.

Download or read book Heart Development and Disease written by Benoit G. Bruneau and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Development of the heart is a complex process and can lead to serious congenital disease if the process goes awry. This book provides a detailed description of the cell lineages involved in heart development and how their migration and morphogenesis are controlled. It also examines the genetic and environmental bases for congenital heart disease and how model systems are revealing more about the processes involved"--