Matrix Metalloproteinases and TIMPs


Book Description

This study covers the sequence information, three-dimensional structures, activation, protein substrates, specificity requirements, inhibition, and biological roles of identified MMPs.




Matrix Metalloproteinases In Health And Disease: Sculpting The Human Body


Book Description

The biochemistry and cell biology of Matrix Metalloproteinases (MMPs) are not necessarily straightforward, but basic information on the history of these enzymes, their various functions that extend far beyond the cleaving of the extracellular matrix, and the complex mechanisms that control their expression are valuable to both scientists and clinicians. This volume summarizes the salient features and functions of MMPs and applies this information in a practical manner in order to understand how they contribute to normal physiology and pathology of selected diseases. Chapters by noted clinicians Jean-Michel Dayer, MD in rheumatology, Jian Cao, MD in oncology, and Peter Libby, MD in cardiology, represent important practical and clinically-oriented contributions.




Composition and Function of the Extracellular Matrix in the Human Body


Book Description

The extracellular matrix (ECM) is an ensemble of non-cellular components present within all tissues and organs of the human body. The ECM provides structural support for scaffolding cellular constituents and biochemical and biomechanical support for those events leading to tissue morphogenesis, differentiation and homeostasis. Essential components of all ECMs are water, proteins and polysaccharides. However, their composition, architecture and bioactivity greatly vary from tissue to tissue in relation to the specific role the ECM is required to assume. This book overviews the role of the ECM in different tissues and organs of the human body.




Matrix Metalloproteinases in Health and Disease


Book Description

Matrix metalloproteinases (MMPs) are members of an enzyme family and are critical for maintaining tissue allostasis. MMPs can catalyze normal turnover of the extracellular matrix (ECM) together with other metalloproteinases such as ADAM (a disintegrin and metalloproteinase) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) families. MMP activity is also regulated by a group of endogenous proteins called tissue inhibitor of metalloproteinases (TIMPs). All these proteins have a pivotal role involving ECM remodelling in normal physiological processes such as wound healing, embryogenesis, angiogenesis, bone remodelling, immunity, and the female reproductive cycle. An imbalance in the expression or activity of MMPs can also have important consequences in diseases such as cancer, cardiovascular disease, peripheral vascular disease, chronic leg ulcers, and multiple sclerosis. In recent years, MMPs have been found to play an important role in the field of precision medicine, as they may serve as biomarkers that may predict an individual's disease predisposition, state, or progression. MMPs are also thought to be a sensible target for molecular therapy. The aim of this Special Issue is to explore the most recent findings in this field that may have an impact in healthcare systems.




Extracellular Matrix Degradation


Book Description

Regulated turnover of extracellular matrix (ECM) is an important component of tissue homeostasis. In recent years, the enzymes that participate in, and control ECM turnover have been the focus of research that touches on development, tissue remodeling, inflammation and disease. This volume in the Biology of Extracellular Matrix series provides a review of the known classes of proteases that degrade ECM both outside and inside the cell. The specific EMC proteases that are discussed include cathepsins, bacterial collagenases, matrix metalloproteinases, meprins, serine proteases, and elastases. The volume also discusses the domains responsible for specific biochemical characteristics of the proteases and the physical interactions that occur when the protease interacts with substrate. The topics covered in this volume provide an important context for understanding the role that matrix-degrading proteases play in normal tissue remodeling and in diseases such as cancer and lung disease.




Matrix Metalloproteinase Inhibitors in Cancer Therapy


Book Description

Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.




Wound Healing


Book Description

Outstanding scientific advances over the last decades unceasingly reveal real complexity of wound-healing process, astonishing in its staged progression, as life is unfolding itself. This natural course of tissue repair seems to bear thousands of overlapping molecular and macroscopic processes that nowadays only start to unfold to our knowledge. The present volume collecting recent scientific references proposes to readers a two-folded audacious goal. First, an updated design of intimate cellular mechanisms is entailed in tissue regeneration that emanates from the first section of the book. Next, a multidisciplinary therapeutic perspective that focuses on macroscopic healing throughout the second part of this work adds clinically integrated observation. Practical diagnostic and treatment information is appended in each chapter that may equally help experienced clinicians or dedicated students and researchers in broadening essential breaking points of their work. It is the wish of all multidisciplinary experts who gather prominent author's panel of this volume to incorporate latest medical reports and compel limits of current understanding for better tissue regeneration, limb salvage, and improved quality of life of our patients.




Capillary Fluid Exchange


Book Description

The partition of fluid between the vascular and interstitial compartments is regulated by forces (hydrostatic and oncotic) operating across the microvascular walls and the surface areas of permeable structures comprising the endothelial barrier to fluid and solute exchange, as well as within the extracellular matrix and lymphatics. In addition to its role in the regulation of vascular volume, transcapillary fluid filtration also allows for continuous turnover of water bathing tissue cells, providing the medium for diffusional flux of oxygen and nutrients required for cellular metabolism and removal of metabolic byproducts. Transendothelial volume flow has also been shown to influence vascular smooth muscle tone in arterioles, hydraulic conductivity in capillaries, and neutrophil transmigration across postcapillary venules, while the flow of this filtrate through the interstitial spaces functions to modify the activities of parenchymal, resident tissue, and metastasizing tumor cells. Likewise, the flow of lymph, which is driven by capillary filtration, is important for the transport of immune and tumor cells, antigen delivery to lymph nodes, and for return of filtered fluid and extravasated proteins to the blood. Given this background, the aims of this treatise are to summarize our current understanding of the factors involved in the regulation of transcapillary fluid movement, how fluid movements across the endothelial barrier and through the interstitium and lymphatic vessels influence cell function and behavior, and the pathophysiology of edema formation. Table of Contents: Fluid Movement Across the Endothelial Barrier / The Interstitium / The Lymphatic Vasculature / Pathophysiology of Edema Formation




Matrix Metalloproteinases and Tissue Remodeling in Health and Disease: Target Tissues and Therapy


Book Description

Matrix Metalloproteinases and Tissue Remodeling in Health and Disease: Target Tissues and Therapy, Volume, Volume 148, the latest volume in the Progress in Molecular Biology and Translational Science series covers a variety of timely topics, with chapters focusing on The Role of Matrix Metalloproteinases in Development, Repair, and Destruction of the Lungs, Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target, Regulation of Matrix Metalloproteinase in the Pathogenesis of Diabetic Retinopathy, Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia, and Matrix Metalloproteinases, Neural Extracellular Matrix, and Central Nervous System Pathology. This volume is the second part of a thematic on matrix metalloproteinases and tissue remodeling in health and disease. It focuses on the role of MMPs in other systems, target tissues, and pathological disorders and the potential benefits of MMP inhibitors in various disorders. Serves as the second part of a thematic on matrix metalloproteinases and tissue remodeling in health and disease Focuses on cardiovascular remodeling Contains contributions from leading authorities on the topics Publishes cutting-edge reviews in molecular biology




Pathophysiological Aspects of Proteases


Book Description

This book provides a comprehensive overview of the multifaceted field of protease in the cellular environment and focuses on the recently elucidated functions of complex proteolytic systems in physiology and pathophysiology. Given the breadth and depth of information covered in the respective contributions, the book will be immensely useful for researchers working to identify targets for drug development. Multidisciplinary in scope, the book bridges the gap between fundamental and translational research, with applications in the biomedical and pharmaceutical industry, making it a thought-provoking read for basic and applied scientists engaged in biomedical research. Proteases represent one of the largest and most diverse families of enzymes known, and we now know that they are involved in every aspect of a given organism’s life functions. Under physiological conditions, proteases are regulated by their endogenous inhibitors. However, when the activity of proteases is not correctly regulated, disease processes such as tumour progression, vascular remodelling, atherosclerotic plaque progression, ulcer, rheumatoid arthritis, Alzheimer’s disease and inflammation can result. Many infective microorganisms require proteases for replication or use them as virulence factors, which has facilitated the development of protease-targeted therapies for a variety of parasitic diseases.