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Introduction: Matrix metalloproteinases (MMPs) are a family ofzinc dependant endopeptidases which selectively degrade components ofthe extracellular matrix. Degradation ofthis matrix is central to several aspects ofcardiovascular disease including adverse left ventricular remodelling, a process which is intimately linked to prognosis. The basis ofthis thesis was to investigate the role ofMMP's and their natural inhibitors tissue inhibitors ofmetalloproteinases (T!MP's) in the process of left ventricular remodelling, clinical heart failure and adverse prognosis post acute myocardial infarction (AMI). Methods: We recruited patients post AMI. Stage I aimed to examine the temporal profile of several MMP's and their relationship with markers ofLV function, volumes and remodelling in a limited population size (n=9I). Stage 2 investigated a more extensive population (n=404), concentrating on a limited number ofMMP's/TIMP's and included clinical follow up to identify subjects with adverse prognosis. All patients were recruited from the CCU units ofthe University Hospitals ofLeicester. All donated venous blood samples at 0-12hrs, 12-24hrs and at 24hr intervals post symptoms until discharge for measurement ofMMP/TIMP's and underwent echocardiographic studies during their index admission and at follow up. During stage 2 all subjects were additionally followed for the clinical endpoints ofdeath or heart failure. We also performed a retrospective analysis ofthe effects ofdiabetes and stress hyperglycaemia on metalloproteinase expression and LV dysfunction post MI. Results: We present convincing data to implicate the MMP system in both LV remodelling and adverse prognosis post AMI. Stage I demonstrates individual temporal profiles of MMP's and presents data on determinants ofMMP expression. We show an association between MMP-9 and LV dysfunction, volumes and remodelling post AMI. Stage 2 confirms both this data and observes similar results for TIMP-I. In addition we demonstrate the association between both MMP-9 and TIMP-I with adverse prognosis and compare with N terminal pro BNP as a prognostic marker. Our retrospective audit ofthe effects ofdiabetes and stress hyperglycaemia is a hypothesis generating chapter which presents association between post MI hyperglycaemia, elevated MMP's and adverse LV function. Summary: Altered MMP/TIMP expression occurs post AMI and is associated with LV dysfunction and remodelling, and with adverse prognosis. The MMP system may represent a potential therapeutic target post AMI.
Discussing recent advances in the field of matrix metalloproteinase (MMP) research from a multidisciplinary perspective, Matrix Metalloproteinase Biologyis a collection of chapters written by leaders in the field of MMPs. The book focuses on the challenges of understanding the mechanisms substrate degradation by MMPs, as well as how these enzymes are able to degrade large, highly ordered substrates such as collagen. All topics addressed are considered in relation to disease progression including roles in cancer metastasis, rheumatoid arthritis and other inflammatory diseases. The text first provides an overview of MMPs, focusing on the history, the development and failures of small molecule inhibitors in clinical trials, and work with TIMPS, the endogenous inhibitors of MMPs. These introductory chapters establish the foundation for later discussion of the recent progress on the design of different types of inhibitors, including novel antibody based therapeutics. The following section emphasizes research using novel methods to further the study of the MMPs. The third and final section focuses on in vivo research, particularly with respect to cancer models, degradation of the extracellular matrix, and MMP involvement in other disease states. Written and edited by leaders in the field, Matrix Metalloproteinase Biology addresses the rapidly growth in MMP research, and will be an invaluable resource to advanced students and researchers studying cell and molecular biology.
Inflammation in Heart Failure, edited by W. Matthijs Blankesteijn and Raffaele Altara, is the first book in a decade to provide an in-depth assessment on the causes, symptoms, progression and treatments of cardiac inflammation and related conditions. This reference uses two decades of research to introduce new methods for identifying inflammatory benchmarks from early onset to chronic heart failure and specifically emphasizes the importance of classifying at-risk subgroups within large populations while determining the patterns of cytokines in such classifications. Further, the book details clinical applications of the pathophysiological mechanisms of heart failure, diagnosis and therapeutic strategies. Inflammation in Heart Failure's breadth of subject matter, easy-to-follow structure, portability, and high-quality illustrations create an accessible benefit for researchers, clinicians and students. - Presents updated information and research on the relevant inflammatory mediators of heart failure to aid in targeting future translational research as well as the improvement of early diagnosis and treatment - Provides research into better understanding the different inflammatory mediators that signal the underlying diseases that potentially lead to heart failure - Contains 20 years of research, offering a brief overview of the topic leading to current opinions on, and treatment of, heart failure - Provides a structured, systematic and balanced overview of the role of inflammation in heart failure making it a useful resource for researchers and clinicians, as well as those studying cardiovascular diseases
Matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes involved in physiological as well as in pathological processes in the human organism. MMPs play a key role in the remodeling of the extracellular matrix. Such a process may occur because of tissue homeostasis, morphogenesis, and tissue repair. However, remodeling could also be a part of many pathological states such as arthritis, cardiovascular diseases, neurodegenerative diseases, or impaired development in congenital anomalies. This book overviews the role of MMPs in different pathologies affecting the human body.
In the joint American College of Cardiology /American Heart Association classification system, Stage B heart failure refers to patients with structural heart disease but no symptoms of heart failure. Preventing progression of heart failure in Stage B patients is a central concern to heart failure specialists, so two issues have been devoted to this topic. Part II focuses on screening to identify patients with Stage B HF and monitoring and therapeutic approaches to patients with a diagnosis of Stage B HF.
Lead editor of Braunwald's Heart Disease, Dr. Douglas L. Mann, and nationally and internationally recognized heart failure expert Dr. G. Michael Felker, bring you the latest, definitive state-of-the art information on heart failure in this outstanding Braunwald's companion volume. Heart Failure, 3rd Edition keeps you current with recent developments in the field, improved patient management strategies, and new drug therapies and implantable devices that will make a difference in your patients' lives and your practice.
In the joint American College of Cardiology /American Heart Association classification system, Stage B heart failure refers to patients with structural heart disease but no symptoms of heart failure. Preventing progression of heart failure in Stage B patients is a central concern to heart failure specialists, so two issues have been devoted to this topic. Part I focuses on an understanding of structural heart disease and the factors that cause progression from risk of heart failure to development of structural changes.
The book provides and intensive overview on exosomes in cardiovascular diseases, its potential as biomarkers, as well as pathological and therapeutic effects. It firstly describes the general aspects of exosomes including the definition, formation and secretion of exosomes and highlight their roles as biomarkers and pathological and therapeutic effects in cardiovascular diseases as well. Secondly, basic aspects of exosomes including the purification methods of exosomes, exosomes content, and functional roles of the cardiovascular exosomes are summarized. Thirdly, exosomes as biomarkers of cardiovascular diseases are overviewed including their roles in diagnosis, prognosis and reaction to therapy. Fourthly, pathological effects of exosomes and therapeutic effects of exosomes are highlighted. Finally, future prospects of exosomes in cardiovascular research would be provided. This is an essential reference for researchers working in cell biology and regeneration, as well as clinicians such as cardiologist.