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The Role of Vinculin in Cardiac Mechanotransduction

The Role of Vinculin in Cardiac Mechanotransduction PDF Author: Amy Lee Hsieh
Publisher:
ISBN: 9781124135182
Category :
Languages : en
Pages : 187

Book Description
Cardiac mechanotransduction is the process by which mechanical signals are transduced into biochemical signals in cardiac myocytes. It is important for moderation of changes in sarcomeric protein assembly, hypertrophic markers, and cell survival. Within a single cardiac myocyte, costameres are complex multi-protein structures which have been shown to be the site where forces generated by cardiac myocytes are transmitted to the external extracellular matrix (ECM) as well as the site where forces externally applied by the ECM are transmitted into the cardiac myocyte. Defects in vinculin and its isoforms, metavinculin, have been implicated in the development of dilated and hypertrophic cardiomyopathy. Due to vinculin's role in contributing to the development of cardiomyopathy and its position in forming a bridge between the ECM and the cytoskeleton, it is hypothesized that vinculin is required for normal mechanotransduction. To study vinculin's role in mechanotransduction, a method using laser tweezers and multifocal multiphoton fluorescence resonance energy transfer (FRET) microscopy was developed. This method allowed the application of calibrated localized forces to cardiomyocytes and the measurement of the cell's response to the force. Results demonstrated that this system can be used to study cardiac mechanotransduction, and that focal adhesion kinase autophosphorylation (FAK-P) as reported by a FRET biosensor changed locally in the cell, but not distally from the site of force application. Additionally, in wildtype cells, FAK-P responses were dependent on cell geometry. These results reveal that types of load depending on orientation of a cell may trigger regulation of hypertrophy. Lastly, using this system, it was determined that anisotropic responses to mechanotransduction as reported by the FAK FRET biosensor is mediated by vinculin. These results reveal the role of the microanatomy of the costamere in determining mechanotransduction events and alterations in hypertrophic signaling. In conclusion, an optically based novel method for studying cardiac mechanotransduction has been developed and it has been used to determine that abnormal vinculin levels alter the biochemical signaling of FAK in response to directionally applied forces. These alterations may contribute to the development of cardiomyopathy and possibly in the development of heart failure.

The Role of Vinculin in Cardiac Mechanotransduction

The Role of Vinculin in Cardiac Mechanotransduction PDF Author: Amy Lee Hsieh
Publisher:
ISBN: 9781124135182
Category :
Languages : en
Pages : 187

Book Description
Cardiac mechanotransduction is the process by which mechanical signals are transduced into biochemical signals in cardiac myocytes. It is important for moderation of changes in sarcomeric protein assembly, hypertrophic markers, and cell survival. Within a single cardiac myocyte, costameres are complex multi-protein structures which have been shown to be the site where forces generated by cardiac myocytes are transmitted to the external extracellular matrix (ECM) as well as the site where forces externally applied by the ECM are transmitted into the cardiac myocyte. Defects in vinculin and its isoforms, metavinculin, have been implicated in the development of dilated and hypertrophic cardiomyopathy. Due to vinculin's role in contributing to the development of cardiomyopathy and its position in forming a bridge between the ECM and the cytoskeleton, it is hypothesized that vinculin is required for normal mechanotransduction. To study vinculin's role in mechanotransduction, a method using laser tweezers and multifocal multiphoton fluorescence resonance energy transfer (FRET) microscopy was developed. This method allowed the application of calibrated localized forces to cardiomyocytes and the measurement of the cell's response to the force. Results demonstrated that this system can be used to study cardiac mechanotransduction, and that focal adhesion kinase autophosphorylation (FAK-P) as reported by a FRET biosensor changed locally in the cell, but not distally from the site of force application. Additionally, in wildtype cells, FAK-P responses were dependent on cell geometry. These results reveal that types of load depending on orientation of a cell may trigger regulation of hypertrophy. Lastly, using this system, it was determined that anisotropic responses to mechanotransduction as reported by the FAK FRET biosensor is mediated by vinculin. These results reveal the role of the microanatomy of the costamere in determining mechanotransduction events and alterations in hypertrophic signaling. In conclusion, an optically based novel method for studying cardiac mechanotransduction has been developed and it has been used to determine that abnormal vinculin levels alter the biochemical signaling of FAK in response to directionally applied forces. These alterations may contribute to the development of cardiomyopathy and possibly in the development of heart failure.

Cardiac Cytoarchitecture

Cardiac Cytoarchitecture PDF Author: Elisabeth Ehler
Publisher: Springer
ISBN: 3319152637
Category : Science
Languages : en
Pages : 320

Book Description
This book presents a collection of expert reviews on different subcellular compartments of the cardiomyocyte, addressing fundamental questions such as how these compartments are assembled during development, how they are changed in and by disease and which signaling pathways have been implicated in these processes so far. As such, it offers the first overview of the cell biology of heart disease of its kind, addressing the needs of cell biology students specializing in vascular and cardiac biology, as well as those of cardiologists and researchers in the field of cell biology.

Post-Genomic Cardiology

Post-Genomic Cardiology PDF Author: José Marín-García
Publisher: Academic Press
ISBN: 0124046428
Category : Medical
Languages : en
Pages : 935

Book Description
In this second edition of Post-Genomic Cardiology, developing and new technologies such as translational genomics, next generation sequencing (NGS), bioinformatics, and systems biology in molecular cardiology are assessed in light of their therapeutic potential. As new methods of mutation screening emerge, both for the genome and for the “epigenome, comprehensive understanding of the many mutations that underlie cardiovascular diseases and adverse drug reactions is within our reach. This book, written by respected cardiologist José Marín-García, features discussion on the Hap-Map: the largest international effort to date aiming to define the differences between our individual genomes. This unique reference further reviews and investigates genome sequences from our evolutionary relatives that could help us decipher the signals of genes, and offers a comprehensive and critical evaluation of regulatory elements from the complicated network of the background DNA. Offers updated discussion of cutting-edge molecular techniques including new genomic sequencing / NGS / Hap-Map / bioinformatics / systems biology approaches Analyzes mitochondria dynamics and their role in cardiac dysfunction, up-to-date analysis of cardio-protection, and cardio-metabolic syndrome Presents recent translational studies, gene therapy, transplantation of stem cells, and pharmacological treatments in CVDs

Cardiac Mechanotransduction

Cardiac Mechanotransduction PDF Author: Matti Weckström
Publisher: Springer Science & Business Media
ISBN: 0387488685
Category : Medical
Languages : en
Pages : 158

Book Description
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.

Piezo Channels

Piezo Channels PDF Author:
Publisher: Academic Press
ISBN: 0128096217
Category : Science
Languages : en
Pages : 350

Book Description
Piezo Channels, Volume 79, the latest volume in the Current Topics in Membranes series provides the necessary membrane research to assist readers in discovering the current state of a particular field and future directions. New chapters in the updated volume include A Tour de Force: The Discovery, Properties, and Function of Piezo Channels, Piezo1 Channels in Vascular Development and the Sensing of Shear Stress, the Origin of the Force: The Force-From-Lipids Principle Applied to Piezo Channels, Genetic Diseases of PIEZO1 and PIEZO2 Dysfunction, and The Structural Basis for Sensing by the Piezo1 Protein. Users of this series will find an up-to-date presentation of the current knowledge in the field of Piezo Channels. Written by leading experts in the field Contains original material, both textual and illustrative, that make it a very relevant reference Presented in a very comprehensive manner Ideal reference for both researchers in the field and general readers who will find this book to be relevant and up-to-date

Mechanotransduction

Mechanotransduction PDF Author:
Publisher: Academic Press
ISBN: 0123983274
Category : Science
Languages : en
Pages : 404

Book Description
Progress in Molecular Biology and Translational Science provides a forum for discussion of new discoveries, approaches, and ideas in molecular biology. It contains contributions from leaders in their fields and abundant references. Volume 126 features in-depth reviews that focus on the tools required to investigate mechanotransduction. Additional chapters focus on how we can use these tools to answer fundamental questions about the interaction of physical forces with cell biology, morphogenesis, and function of mature structures. Chapters in the volume are authored by a unique combination of cell biologists and engineers, providing a range of perspectives on mechanotransduction. Provides a unique combination of perspectives from biologists and engineers Engaging to people of many training backgrounds

Stretch Intensity and the Inflammatory Response: A Paradigm Shift

Stretch Intensity and the Inflammatory Response: A Paradigm Shift PDF Author: Nikos C. Apostolopoulos
Publisher: Springer
ISBN: 3319968009
Category : Science
Languages : en
Pages : 231

Book Description
In this manuscript, practitioners and students who are concerned with sports and rehabilitation medicine, kinesiology, as well as coaches and athletes, are introduced to numerous concepts, including mechanotransduction, inflammation, pro- and anti-inflammatory cytokines, calpains, the extracellular matrix, neutrophils and macrophages, and their relevance to stretching, particularly stretching intensity. Although the quantitative parameters of training, duration, and frequency are important, it is the qualitative criterion of intensity (“how much”) that the author suggests is ultimately of greater concern. Intensity, the rate and magnitude of force, may be responsible for the proper recovery, regeneration, and adaptation of the musculoskeletal tissues from training, competition, or rehabilitation from injuries. Research suggests that too much force results in the stimulation of an inflammatory response, one associated with a biochemical feedback emerging from a mechanical stimulus. The intent of this manuscript is twofold: to initiate the discussion of the importance of stretching intensity with regard to proper recovery, regeneration, and adaptation, and to suggest that researchers need to explore its potential role in addressing numerous inflammatory (RA) and non-inflammatory (OA, recurrent tendinitis etc.) musculoskeletal conditions as well.

Heart Failure: A Companion to Braunwald's Heart Disease E-Book

Heart Failure: A Companion to Braunwald's Heart Disease E-Book PDF Author: G. Michael Felker
Publisher: Elsevier Health Sciences
ISBN: 0323609880
Category : Medical
Languages : en
Pages : 784

Book Description
Up-to-date, authoritative and comprehensive, Heart Failure, 4th Edition, provides the clinically relevant information you need to effectively manage and treat patients with this complex cardiovascular problem. This fully revised companion to Braunwald’s Heart Disease helps you make the most of new drug therapies such as angiotensin receptor neprilysin inhibitors (ARNIs), recently improved implantable devices, and innovative patient management strategies. Led by internationally recognized heart failure experts Dr. G. Michael Felker and Dr. Douglas Mann, this outstanding reference gives health care providers the knowledge to improve clinical outcomes in heart failure patients. Focuses on a clinical approach to treating heart failure, resulting from a broad variety of cardiovascular problems. Covers the most recent guidelines and protocols, including significant new updates to ACC, AHA, and HFSA guidelines. Covers key topics such as biomarkers and precision medicine in heart failure and new data on angiotensin receptor neprilysin inhibitors (ARNIs). Contains four new chapters: Natriuretic Peptides in Heart Failure; Amyloidosis as a Cause of Heart Failure; HIV and Heart Failure; and Neuromodulation in Heart Failure. Covers the pathophysiological basis for the development and progression of heart failure. Serves as a definitive resource to prepare for the ABIM’s Heart Failure board exam. 2016 British Medical Association Award: First Prize, Cardiology (3rd Edition).

Myofibrillogenesis

Myofibrillogenesis PDF Author: Dipak K. Dube
Publisher: Springer Science & Business Media
ISBN: 9780817642266
Category : Science
Languages : en
Pages : 304

Book Description
Myofibrillogenesis has been studied extensively over the last 100 years. Until recently, we have not had a comprehensive understanding of this fundamental process. The emergence of new technologies in molecular and cellular biology, combined with classical embryology, have started to unravel some of the complexities of myofibril assembly in striated muscles. In striated muscles, the contractile proteins are arranged in a highly ordered three dimensional lattice known as the sarcomere. The assembly of a myofibril involves the precise ordering of several proteins into a linear array of sarcomeres. Multiple isoforms in many of these proteins further complicate the process, making it difficult to define the precise role of each component. This volume has been compiled as a comprehensive reference on myofibrillogenesis. In addition, the book includes reviews on myofibrillar disarray under various pathological conditions, such as familial hypertrophic cardiomyopathy (FHC), and incorporates a section on the conduction system in the heart. Much of the information in this volume has not been described elsewhere. Presented in a manner to be of value to students and teachers alike, "Myofibrillogenesis" will be an invaluable reference source for all in the fields of muscle biology and heart development.

Functional Organization of Vertebrate Plasma Membrane

Functional Organization of Vertebrate Plasma Membrane PDF Author:
Publisher: Elsevier
ISBN: 0124171168
Category : Science
Languages : en
Pages : 393

Book Description
Current Topics in Membranes is targeted toward scientists and researchers in biochemistry and molecular and cellular biology, providing the necessary membrane research to assist them in discovering the current state of a particular field and in learning where that field is heading. This volume covers recent breakthroughs in understanding the molecular and cellular basis for patterning vertebrate plasma membranes. A special emphasis is placed on physiological function with chapters covering signaling in the nervous system and heart, vision, and the immune system. consolidates subjects normally dispersed in the literature presents in one volume a subject that has undergone a recent molecular revolution authors are primary contributors and in some cases the founding figures in their fields