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.
Endothelial Signaling, Mechanotransduction, Vascular Biology and Atherosclerosis, Volume 87, the latest release in the Current Topics in Membranes series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of timely topics. Each chapter is written by an international board of authors. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in "Current Topics in Membranes" series Updated release includes the latest information on Endothelial Signaling, Mechanotransduction, Vascular Biology and Atherosclerosis
This book presents the latest findings in the field of research of mechanosensitivity and mechanotransduction in different cells and tissues. Mechanosensitivity and mechanotransduction of the heart and vascular cells, in the lung, in bone and joint tissues, in sensor systems and in blood cells are described in detail. This Volume focuses on molecular mechanisms of mechanosensitivity and mechanotransduction via cytoskeleton. Integrin-mediated mechanotransduction, the role of actin cytoskeleton and the role of other cytoskeletal elements are discussed. It contains a detailed description of several stretch-induced signaling cascades with multiple levels of crosstalk between different pathways. It contains a description of the role of nitric oxide in regulation of cardiac activity and in regulation of mechanically gated channels in the heart. In the heart mechanical signals are propagated into the intracellular space primarily via integrin-linked complexes, and are subsequently transmitted from cell to cell via paracrine signaling. Biochemical signals derived from mechanical stimuli activate both acute phosphorylation of signaling cascades, such as in the PI3K, FAK, and ILK pathways, and long-term morphological modii cations via intracellular cytoskeletal reorganization and extracellular matrix remodelling. Cellular and molecular effects of mechanical stretch on vascular cells are also discussed. This Volume highlights the role of mechanotransduction in the lung, in bone and joint tissues. For the first time mechanosensitivity and mechanotransduction in blood cells are discussed. It contains new insights into mechanosensitive K+ channels functioning in mouse B lymphocytes. This book is a unique collection of reviews outlining current knowledge and future developments in this rapidly growing field. Currently, investigations of the molecular mechanisms of mechanosensitivity and mechanotransduction are focused on several issues. The majority of studies investigate intracellular signaling pathways. Knowledge of the mechanisms which underlie these processes is necessary for understanding of the normal functioning of different organs and tissues and allows to predict changes, which arise due to alterations of their environment. Possibly such knowledge will allow the development of new methods of artificial intervention and therapies. This book brings up the problem closer to the experts in related medical and biological sciences as well as practicing doctors besides just presenting the latest achievements in the field.
This timely review of heart mechanosensitivity examines tissues at the molecular, biological, bio-physical, physiological and pharmaceutical levels. New insight on the electromechanical properties of cardiac tissue is supported with experimental results.
This volume of the series Cardiac and Vascular Biology presents the most relevant aspects of vascular mechanobiology along with many more facets of this fascinating, timely and clinically highly relevant field. Mechanotransduction, mechanosensing, fluid shear stress, hameodynamics and cell fate, are just a few topics to name. All important aspects of vascular mechanobiology in health and disease are reviewed by some of the top experts in the field. This volume, together with a second title on cardiac mechanobiology featured in this series, will be of high relevance to scientists and clinical researchers in the area of vascular biology, cardiology and biomedical engineering.
Translational Cardiology: Molecular Basis of Cardiac Metabolism, Cardiac Remodeling, Translational Therapies and Imaging Techniques provides an up-to-date introduction to the role circadian rhythms, cardiac plasticity, and mechanotransduction play in the heart, while at the same time introducing new developments in cellular, viral, and non-biologic therapies that are in the process of being developed. Importantly, the focus of this book is on topics that, due to their novelty, are largely not covered in the other major textbooks. A special emphasis is placed on the molecular basis of cardiac metabolism, new concepts in cardiac remodeling, and translational therapies and imaging techniques currently under development for clinical use. The chapters are written by experts from diverse clinical and biomedical research backgrounds. Translational Cardiology: Molecular Basis of Cardiac Metabolism, Cardiac Remodeling, Translational Therapies and Imaging Techniques simplifies the complexity of the molecular basis of disease by focusing on patient-oriented disease mechanisms and therapies and is of great value to a broad audience including physicians (e.g. cardiologists, cardiovascular surgeons, pathologists) as well as translational biomedical researchers in a wide range of disciplines.
This book presents the latest findings in the field of cardiac mechanobiology in health and disease. Cardiac mechanobiology provides knowledge of all aspects of mechanobiology of the heart. Cardiomyogenesis is discussed as well as the mechanobiology of cardiac remodeling and regeneration. The molecular mechanisms of mechanoperception and mechanotransduction in cardiomyocytes are explained, as well as stretch induced differentiation of cardiomyocytes derived from induced pluripotent stem cells. This volume of the series Cardiac and Vascular Biology complements the volume Vascular Mechanobiology in Physiology and Disease (volume 8) published in this series. The book is aimed at clinicians as well as researchers in cardiovascular biology, bioengineering and biophysics, and also represents an educational resource for young researchers and students in these fields.
This dissertation investigated the role of biomechanics in two physiological systems, the heart and bone. Biomechanics motivates the study and characterization of how cells sense external forces and convert these signals into an intracellular response in a process called mechanotransduction. Three independent studies were designed with the goal of applying mechanical forces that mimic the in vivo microenvironment of either the heart or bone. The aim of these studies was to better under the mechanisms driving cellular processes, including cardiac myocyte differentiation and osteoblast mechanotransduction. The first study presents the design and implementation of tissue engineering approach to stem cell-based myocardial therapy. Three dimensional engineered heart tissue was formed by suspending human embryonic stem cell-derived cardiac myocytes isolated from beating embryoid bodies in a soluble extracellular matrix, and an in vitro mechanical conditioning regimen was applied at physiological levels of myocardial strain. The viability of the engineered stem cell tissue was monitored in vitro and in vivo for up to 8 weeks using molecular imaging of reporter gene activity. The application of cyclic mechanical strain in vitro resulted in cellular alignment along the axis of strain and an elongated cellular morphology with a high nuclear to cytoplasmic ratio, typical of neonatal cardiac myocytes, as well as increased expression of cardiac troponin I, in comparison to static controls. Analysis of the in vitro and in vivo bioluminescence imaging data demonstrated the viability of engineered heart tissue constructs; however, histology results showed immature cells within the implanted constructs, suggesting an inability of the stem cell-derived cardiac precursors to maintain a cardiac phenotype in vivo, as well the inherent inefficiency of the beating embryoid body method to identify and isolate cardiac myocyte precursors. The functional shortcomings exhibited by the embryoid body-based differentiation of embryonic stem cell-derived cardiac myocytes in the first study motivated further refinement of cardiac myocyte differentiation techniques. Therefore, the second study executed the design and fabrication of a microelectromechanical platform to study the role of electrical and mechanical stimulation in cardiac myocyte differentiation. The fabrication process used a combination of soft lithography and traditional microfabrication techniques to pattern thin film metal electrodes on an elastomeric polymer membrane. The completed device enabled coupled characterization and imaging of cardiac myocytes precursors, and the ability to assess the range of mechanical forces, up to 10% equibiaxial strain, that may induce or maintain a cardiac fate. Electrical continuity was demonstrated under static conditions but not under strain, and improvements in metal deposition and adhesion could address this performance defect. Beating clusters containing human embryonic stem cell-derived cardiac myocytes were plated on fabricated membranes, uncoated and coated with Matrigel, and cell viability was monitored using contrast microscopy. The third study transitioned to a different mechanical model of physiological forces, which was the application of oscillatory fluid flow-mediated fluid shear stress generated by the loading and unloading of bone. Specifically, the role of focal adhesion kinase, a protein tyrosine kinase recruited at focal adhesions and a major mediator of integrin signaling pathways, was studied in osteoblast mechanotransduction. The biochemical and transcriptional response of focal adhesion kinase mutant osteoblasts to physiological levels of shear stress induced by oscillatory fluid flow was impaired as measured by prostaglandin E2 release and cyclooxygenase-2 gene expression. Restoration of focal adhesion kinase expression with site-specific mutations at two tyrosine phosphorylation sites demonstrated that phosphorylation events play a role in prostaglandin release following oscillatory fluid flow. In conclusion, the role of mechanical forces, including the effect of cyclic mechanical strain in human embryonic stem cell-derived cardiac myocyte tissue engineering and the fluid shear stress-induced response of focal adhesion kinase mutant osteoblasts, was successfully demonstrated and quantified in this dissertation.
The microcirculation is highly responsive to, and a vital participant in, the inflammatory response. All segments of the microvasculature (arterioles, capillaries, and venules) exhibit characteristic phenotypic changes during inflammation that appear to be directed toward enhancing the delivery of inflammatory cells to the injured/infected tissue, isolating the region from healthy tissue and the systemic circulation, and setting the stage for tissue repair and regeneration. The best characterized responses of the microcirculation to inflammation include impaired vasomotor function, reduced capillary perfusion, adhesion of leukocytes and platelets, activation of the coagulation cascade, and enhanced thrombosis, increased vascular permeability, and an increase in the rate of proliferation of blood and lymphatic vessels. A variety of cells that normally circulate in blood (leukocytes, platelets) or reside within the vessel wall (endothelial cells, pericytes) or in the perivascular space (mast cells, macrophages) are activated in response to inflammation. The activation products and chemical mediators released from these cells act through different well-characterized signaling pathways to induce the phenotypic changes in microvessel function that accompany inflammation. Drugs that target a specific microvascular response to inflammation, such as leukocyte-endothelial cell adhesion or angiogenesis, have shown promise in both the preclinical and clinical studies of inflammatory disease. Future research efforts in this area will likely identify new avenues for therapeutic intervention in inflammation. Table of Contents: Introduction / Historical Perspectives / Anatomical Considerations / Impaired Vasomotor Responses / Capillary Perfusion / Angiogenesis / Leukocyte-Endothelial Cell Adhesion / Platelet-Vessel Wall Interactions / Coagulation and Thrombosis / Endothelial Barrier Dysfunction / Epilogue / References
