Fibrosis in Disease

This book serves as a state-of-the-art resource for physicians and translational medical researchers alike who are interested in the rapidly evolving field of fibroproliferative diseases. It provides new insight into the fundamental mechanisms of classic fibrotic pathophysiologic processes like myocardial infarction, idiopathic pulmonary fibrosis, chronic kidney disease, wound healing, and systemic sclerosis. It also highlights the many new areas of therapeutic investigation currently underway. Lastly, it touches upon newly emerging fields andinvestigates the role of fibrosis in macular degeneration and cancer metastasis.

Chapters are written by established experts in their fields, including clinicians, cardiologists, cardiovascular surgeons, pathologists, general practitioners, and translational biomedical researchers in a wide range of disciplines. However, the material also applies to a broader audience, including medical residents, fellows, and M.D. or Ph.D. post-doctoral research fellows. While comprehensive, this book presents the material in a manner that simplifies the complex pathophysiologic mechanisms that underlie common fibroproliferative diseases while making it appealing to a broad audience.

Autorentext

Monte S. Willis
Indiana University School of Medicine
Indiana Center for Musculoskeletal Health
Department of Pathology & Laboratory Medicine
Krannert Institute of Cardiology
Indianapolis, IN
USA

Cecelia C. Yates
University of Pittsburgh
School of Nursing
Pittsburgh, PA
USA

Jonathan C. Schisler
University of North Carolina
McAllister Heart Institute
Department of Pharmacology
Department of Pathology and Lab Medicine
Chapel Hill, NC
USA

Zusammenfassung

Fibroproliferative diseases are a broad spectrum of entities from organ-specific involvement (e.g., pulmonary, heart, liver, and kidney fibrosis) to multi-system diseases such as systemic sclerosis and sclerodermatous graft vs. host disease. These diseases also encompass pathophysiologies not readily recognizably related, such as macular degeneration and cancer metastasis. Fibroproliferative diseases are a leading cause of morbidity and mortality and can affect all tissues and organ systems. Remarkable progress in elucidating the pathogenesis of these common diseases with fibrotic components, including the critical roles of myofibroblasts and the molecular mechanisms driving the transcriptional activation involved in the induction of fibrosis. As the importance of these processes is realized in the long-term recovery and treatment of diseases, effective anti-fibrotic therapies targeting the underlying ongoing disease processes are lacking.

The complexity of discovering and applying therapies to fibroproliferative disease may be due to the diversity of the systems the pathogenesis of disease itself involves. By nature, fibroproliferative diseases are interdisciplinary, involving multiple cell types (organ-specific epithelial cells), immune cells, endothelial cells, and fibroblasts. Bone marrow, cytokines, and organ-specific pathologies further speckle both the clinical and scientific disciplines in such a way that communication is often limited to the clinical or scientific tribes we live in, despite the greatest access to information known to man available today. Therefore, the primary focus of this text is to bring together authors from a diversity of both clinical, scientific, and therapeutic backgrounds for readers to more fully appreciate that fantastic platform that is available to build upon to lessen the isolation of the clinical and scientific disciplines. With advances in the discovery of pre-clinical therapeutic targets (at least 20+ to date) involving TGF-beta (and other cytokines), transcription factors, and downstream kinases, it's important to both recognize the broader impact and potential opportunities that exist even today.

This book will serve as a state-of-the-art resource for physicians and translational medical researchers alike who are interested in the rapidly evolving field of fibroproliferative diseases. The book will provide new insight into the fundamental mechanisms of classic fibrotic pathophysiologic processes like myocardial infarction, idiopathic pulmonary fibrosis, chronic kidney disease, wound healing, and systemic sclerosis. It will also highlight the many new areas of therapeutic investigation currently underway. Lastly, we will touch upon newly emerging fields investigating the role of fibrosis in macular degeneration and cancer metastasis.

The chapters will be written by established experts in their fields, including clinicians (cardiologists, cardiovascular surgeons, pathologists, and general practitioners) and translational biomedical researchers in a wide range of disciplines. However, the material will certainly have a broader audience including medical residents, fellows, and general practitioners as well as M.D. or Ph.D. post-doctoral research fellows. While comprehensive, we'll attempt to present the material in a manner that simplifies the complex pathophysiologic mechanisms that underlie common fibroproliferative diseases while making it appealing to a broad audience.

Inhalt

Introduction.- The Role of Chemokines in Fibrotic dermal remodeling and wound healing.- Fibrosis and immune dysregulation in systemic sclerosis.- Macrophage Plasticity in Skin Fibrosis.- Fibrotic Signaling in the Lung.- Pulmonary Matrikines: Origin, Function and Contribution to Fibrotic and Non-Fibrotic Lung Disease.- The Role of Mast Cells in the Pathophysiology of Pulmonary Fibrosis.- PERICYTES AND T CELLS IN LUNG INJURY AND FIBROPROLIFERATION.- Emerging Therapeutic Targets and Therapies in Idiopathic Pulmonary Fibrosis.- Dynamic reciprocity- the role of the extracellular matrix microenvironment in amplifying and sustaining pathological lung fibrosis.- Fibrotic Signaling in Cardiomyopathies.- WNT SIGNALING AND CARDIAC FIBROSIS.- Matrix metalloproteinase-9-dependent mechanisms of reduced contractility and increased stiffness in the aging heart.- Using peptidomics to identify extracellular matrix-derived peptides as novel therapeutics for cardiac disease.- Vascular Fibrosis and Disease.- Liver Fibrosis: Current Approaches and Future Directions for Diagnosis and Treatment.- Tipping the balance from angiogenesis to fibrosis in chronic kidney disease.- Fibrotic Remodeling in Exudative (Wet) Macular Degeneration.