Endothelial Cell CEACAM1 Regulates Fibrosis PDF Download

Author: Raghd Abu Helal
Publisher:
ISBN:
Category : Aorta
Languages : en
Pages : 158

View

Book Description
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a transmembrane glycoprotein that is expressed in a variety of tissues, including liver, heart, aorta, prostate, small intestine, and to a lesser extent the white adipose tissue. It is also expressed in several cells such as endothelial, immune, and epithelial cells. Many functions have been assigned to CEACAM1. These include maintaining insulin sensitivity, vascular homeostasis, as well as mediating cellular adhesion and immune function. Moreover, upon its phosphorylation by the insulin receptor tyrosine kinase, CEACAM1 upregulates receptor-mediated insulin endocytosis and degradation, a main mechanism of insulin clearance in hepatocytes. It also enables a negative acute effect of insulin pulses on fatty acid synthase activity in hepatocytes. This emphasizes the dual role of CEACAM1 in promoting insulin clearance and regulating lipid metabolism to maintain insulin sensitivity. Hepatic CEACAM1 levels have been shown to be reduced in obese subjects with nonalcoholic fatty liver disease (NAFLD), regardless of whether they also exhibit type 2 diabetes or not. Studies on mice with global null deletion of Ceacam1 gene, and mice with liver-specific inactivation of CEACAM1 exhibited hyperinsulinemia resulting from impaired hepatic insulin clearance and systemic insulin resistance. In addition, global Ceacam1 mutant mice manifested spontaneous steatohepatitis and chicken-wire bridging fibrosis, one of the distinct features of human NASH. Moreover, patients with NASH are at a higher risk of developing atherosclerosis a chronic inflammatory reaction that takes place in the sub-endothelium of the aorta. In fact, both of NASH and atherosclerosis are characterized by fat accumulation and inflammation leading to fibrosis. However, the molecular mechanisms underlying the etiology and progression of both diseases has not been well-elucidated. Hence, using mouse models of tissue-specific gain-of-function or loss-of-function mechanisms, we investigated CEACAM1-dependent signaling pathways leading to these cardiometabolic conditions.

Author: Kelly J. Ledford
Publisher:
ISBN:
Category :
Languages : en
Pages : 118

View

Book Description
The metabolic syndrome is associated with an increased risk for cardiovascular disease. Defining a mechanistic link between these diseases has been limited by the lack of an experimental model that completely mimics the human state. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin and lipid metabolism in liver, down regulates inflammatory response in activated T-lymphocytes, modulates epidermal growth factor receptor (EGFR) mediated signalling, and preserves the endothelium through its role in angiogenesis. Null mutation of Ceacam1 (Cc1-/- )results in insulin resistance due to impaired insulin clearance, resulting in visceral obesity, dyslipidemia, and hepatic steatosis due to elevated triglyceride and cholesterol synthesis, and high plasma triglyceride and fatty acid levels. The goal of this work was to test whether loss of CEACAM1 also results in cardiovascular disease. We herein characterized the cardiovascular phenotype of the (Cc1-/- )mice. Histological examination of the vasculature revealed that at six months the (Cc1-/- )mice develop spontaneous atherosclerotic lesions. In addition, six month old (Cc1-/- )mice exhibit modest plasma hypercholesterolemia, elevated markers of vascular inflammation measured by quantitative real-time PCR, oxidative stress, and endothelial dysfunction all factors associated with atherosclerosis. We herein report that the (Cc1-/- )mice provide a novel model to study the mechanistic relationship between metabolic abnormalities, endothelial dysfunction, and atherosclerosis, and also highlight CEACAM1 with a potential mechanistic role linking metabolic abnormalities, endothelial dysfunction, and atherosclerosis. Six month old (Cc1-/- )mice were also found to be hypertensive, indicating that they are a novel mouse model of the metabolic syndrome. This rise in blood pressure was associated with an elevated activation of the renin angiotensin system (RAS). Further examination of the (Cc1-/- )mice kidneys revealed evidence of renal inflammation and fibrosis. This data highlights CEACAM1 as a novel mechanistic link between metabolic abnormalities, hypertension, and the up regulation of the RAS. The presented work promotes the (Cc1-/- )mouse as a novel model to investigate the mechanistic link between the metabolic syndrome and the pathogenesis of the cardiovascular diseases, as well as identify CEACAM1 as a potential molecular target of these disorders.

Author: Z. Kmiec
Publisher: Springer Science & Business Media
ISBN: 3642565530
Category : Science
Languages : en
Pages : 154

View

Book Description
It is only during the last decade that the functions of sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, pit cells and other intrahepatic lymphocytes have been better understood. The development of methods for isolation and co-culturing various types of liver cells has established that they communicate and cooperate via secretion of various intercellular mediators. This monograph summarizes multiple data that suggest the important role of cellular cross-talk for the functions of both normal and diseased liver. Special features of the book include concise presentation of the majority of detailed data in 19 tables. Original schemes allow for the clear illustration of complicated intercellular relationships. This is the first ever presentation of the newly emerging field of liver biology, which is important for hepatic function in health and disease and opens new avenues for therapeutic interventions.

Author: Rudolf Ludwig Karl Virchow
Publisher: Legare Street Press
ISBN: 9781015708761
Category : Health & Fitness
Languages : en
Pages : 0

View

Book Description
This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work is in the "public domain in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant.

Author: Victor R. Preedy
Publisher: Springer
ISBN: 9789400776746
Category : Medical
Languages : en
Pages : 0

View

Book Description
In the past decade there has been a major sea change in the way disease is diagnosed and investigated due to the advent of high throughput technologies, such as microarrays, lab on a chip, proteomics, genomics, lipomics, metabolomics etc. These advances have enabled the discovery of new and novel markers of disease relating to autoimmune disorders, cancers, endocrine diseases, genetic disorders, sensory damage, intestinal diseases etc. In many instances these developments have gone hand in hand with the discovery of biomarkers elucidated via traditional or conventional methods, such as histopathology or clinical biochemistry. Together with microprocessor-based data analysis, advanced statistics and bioinformatics these markers have been used to identify individuals with active disease or pathology as well as those who are refractory or have distinguishing pathologies. New analytical methods that have been used to identify markers of disease and is suggested that there may be as many as 40 different platforms. Unfortunately techniques and methods have not been readily transferable to other disease states and sometimes diagnosis still relies on single analytes rather than a cohort of markers. There is thus a demand for a comprehensive and focused evidenced-based text and scientific literature that addresses these issues. Hence the formulation of Biomarkers in Disease The series covers a wide number of areas including for example, nutrition, cancer, endocrinology, cardiology, addictions, immunology, birth defects, genetics, and so on. The chapters are written by national or international experts and specialists.

Author: Christopher Griffiths
Publisher: John Wiley & Sons
ISBN: 1118441176
Category : Medical
Languages : en
Pages : 4992

View

Book Description
2017 PROSE Award Winner - Multivolume Reference/Science The world's number 1 dermatology information resource Universally respected, Rook's Textbook of Dermatology is the most comprehensive, definitive and best-illustrated reference work for dermatologists of all levels worldwide and has been at the forefront of international dermatology publishing since first appearing in 1968. The Ninth Edition has been radically re-engineered to match the modern day challenges faced by dermatologists. Once again it has been published as a combined digital and print resource, but with a new online platform enabling easier and faster navigation. A common structure to describe and discuss each disorder has been adopted throughout, whilst maintaining the depth of information for which Rook is renowned. A high priority has been placed on the ease of extracting key information quickly: diagnostic algorithms and management ladders help the reader choose appropriate treatment strategies. More images than ever – over 5000 in total – aid diagnosis by displaying variations in disease manifestations according to body location, skin type and severity. The section on aesthetic dermatology has been greatly expanded with more coverage of procedures in this rapidly developing field. Rook's Textbook of Dermatology, Ninth Edition provides you with: The very best content from the number one brand in dermatology – an essential consultation tool for all dermatologists An outstanding combined digital/print resource, exhaustively covering every dermatological disorder A complete overhaul of its content – each disorder now follows a consistent templated approach A fresh approach to the classification of disorders and organization of chapters, of which there are now 160 instead of 80, all organised into 14 logical sections A newly designed sophisticated online platform with a fast and powerful digital search functionality – search by keyword, disorder or chapter or consult the online image database and get expert clinical advice more quickly than ever Lavishly illustrated chapters with over 5000 colour images showing variation in disease patterns by body location, skin type and severity Comprehensive coverage of medical, surgical and aesthetic dermatology, as well as the basic science underpinning the field An experienced British editorial team working with distinguished international authors and associate editor Greater emphasis than before on clinical studies/trials, society guidelines and the latest ICD codes While key references remain in the printed version, thousands more are cited in the book and can be accessed online, where each is hyperlinked to the relevant text Rook’s Textbook of Dermatology, Ninth Edition is the complete dermatology reference work. More comprehensive than ever, with more images, more disorders covered and faster, more dynamic and wider digital search functionality. It is an essential resource for the modern day dermatologist, whether experienced or at the beginning of a career in dermatology.

Author: Monte S. Willis
Publisher: Springer
ISBN: 3319981439
Category : Medical
Languages : en
Pages : 474

View

Book Description
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.

Author: Yoram Groner
Publisher: Springer
ISBN: 9811032335
Category : Medical
Languages : en
Pages : 518

View

Book Description
This volume provides the reader with an overview of the diverse functions of the RUNX family of genes. As highlighted in the introduction and several of the 29 chapters, humans and other mammals have three RUNX genes that are known to play specific roles in blood, bone and neuronal development. However, their evolutionary history has recently been traced back to unicellular organisms and their involvement in many well-known signaling pathways (Wnt, TGFb, Notch, Hippo) is indicative of a more general function in cell biology. Their documented roles in cell fate decisions include control of proliferation, differentiation, survival, senescence and autophagy. The pleiotropic effects of RUNX in development are mirrored in cancer, where RUNX genes can function as oncogenes that collaborate strongly with Myc family oncogenes or as tumour suppressor genes. In the latter role, they display hallmarks of both ‘gatekeepers’ that modulate p53 responses and ‘caretakers’ that protect the genome from DNA damage. Several chapters focus on the importance of these genes in leukemia research, where RUNX1 and CBFB are frequently affected by chromosomal translocations that generate fusion oncoproteins, while recent studies suggest wider roles for RUNX modulation in solid cancers. Moreover, RUNX genes are intimately involved in the development and regulation of the immune system, while emerging evidence suggests a role in innate immunity to infectious agents, including HIV. At the biochemical level, the RUNX family can serve as activators or repressors of transcription and as stable mediators of epigenetic memory through mitosis. Not surprisingly, RUNX activity is controlled at multiple levels, this includes miRNAs and a plethora of post-translational modifications. Several chapters highlight the interplay between the three mammalian RUNX genes, where cross-talk and partial functional redundancies are evident. Finally, structural analysis of the RUNX/CBFB interaction has led to the development of small molecule inhibitors that provide exciting new tools to decipher the roles of RUNX in development and as targets for therapy. This volume provides a compendium and reference source that will be of broad interest to cancer researchers, developmental biologists and immunologists.

Author: Alan R. Saltiel
Publisher: Springer Science & Business Media
ISBN: 0387722041
Category : Medical
Languages : en
Pages : 223

View

Book Description
More than 18 million people in the United States have diabetes mellitus, and about 90% of these have the type 2 form of the disease. This book attempts to dissect the complexity of the molecular mechanisms of insulin action with a special emphasis on those features of the system that are subject to alteration in type 2 diabetes and other insulin resistant states. It explores insulin action at the most basic levels, through complex systems.

Author: G. Berx
Publisher: Springer Science & Business Media
ISBN: 3540209417
Category : Medical
Languages : en
Pages : 479

View

Book Description
This book provides an overview of the main topics of current cell adhesion research including structural analyses of cell adhesion molecules and studies to their functional role in vitro and in vivo. The present volume focuses on the four major families of cell-adhesion receptors, i.e. the cadherins, the integrins, the Ig-superfamily and the selectin-based adhesion system which are discussed in detail by numerous experts in the field.