Descripción
Description
A valuable study of the science behind the medicine, Muscle: Fundamental Biology and Mechanisms of Disease brings together key leaders in muscle biology. These experts provide state-of-the-art insights into the three forms of muscle–cardiac, skeletal, and smooth–from molecular anatomy, basic physiology, disease mechanisms, and targets of therapy. Commonalities and contrasts among these three tissue types are highlighted. This book focuses primarily on the biology of the myocyte.
Individuals active in muscle investigation–as well as those new to the field–will find this work useful, as will students of muscle biology. In the case of hte former, many wish to grasp issues at the margins of their own expertise (e.g. clinical matters at one end; molecular matters at the other), adn this book is designed to assist them. Students, postdoctoral fellows, course directors and other faculty will find this book of interest. Beyond this, many clinicians in training (e.g. cardiology fellows) will benefit.
Key Features
- The only resource to focus on science before the clinical work and therapeutics
- Tiered approach to subject: discussion first of normal muscle function through pathological/disease state changes, and ending each section with therapeutic interventions
- Coverage of topics ranging from basic physiology to newly discovered molecular mechanisms of muscle diseases for all three muscle types: cardiac, skeletal, and smooth.
Readership
The primary audience for this work is entry level and experienced researchers, practicing clinicians, postdocs, graduate students, and medical students across molecular and muscle medicine, developmental biology, molecular biology, cell biology, physiology, pathology, pharmacology, cardiology, translational medicine and biomedicine.
Table of Contents
List of Contributors
Acknowledgments
VOLUME 1
Part I: Introduction
Chapter 1. An Introduction to Muscle
Cardiac Muscle
Skeletal Muscle
Smooth Muscle
Common Molecular Mechanisms
Summary
Chapter 2. A History of Muscle
Introduction
Early Observations
Animal Spirits and the Vital Force
Electrical Activation
Energy Utilization: Work and Heat
Energy Production: Metabolism
Contractile Proteins
The Sliding-Filament Hypothesis
Calcium, Excitation–Contraction Coupling, Relaxation
Skeletal, Cardiac, and Smooth Muscle
Conclusion
REFERENCES
Part II: Cardiac Muscle
Section A: Basic Physiology
Chapter 3. Cardiac Myocyte Specification and Differentiation
Early Fate Decisions in Commitment of Mesoderm to the Cardiac Muscle Lineage
Cardiac Progenitors Arise from Two Molecularly Distinct “Heart Fields”
Differentiation of Cardiac Progenitors into Functional Myocytes
Conclusions
REFERENCES
Chapter 4. Transcriptional Control of Cardiogenesis
Overview of Transcription Factors Necessary for Heart Development
Transcriptional Regulation of Cardiac Morphogenesis
Transcriptional Regulation of Cardiac Conduction System Development
Transcriptional Regulation of Cardiomyocyte Proliferation
Summary and Perspectives
Acknowledgments
REFERENCES
Chapter 5. Cardiomyocyte Ultrastructure
Introduction
Myocyte Architecture
Non-Myocyte Tissue Compartment
Regional Variation in Structure
REFERENCES
Chapter 6. Overview of Cardiac Muscle Physiology
Introduction
The Cardiac Pump
Regulation of the Cardiac Pump
Basis for the Cardiac Output Changes During Exercise
Bibliography
Chapter 7. Ionic Fluxes and Genesis of the Cardiac Action Potential
Ionic Flux in Cardiomyocytes
Membrane Transporters
Action Potential Genesis
Action Potential Propagation – Electrical Communication
Acknowledgments
REFERENCES
Chapter 8. G-Protein-Coupled Receptors in the Heart
Introduction
Overview of G-Protein-Coupled Receptor Signaling
Cardiac G-Protein-Coupled Receptors
The Future of GPCR Drug Targeting
REFERENCES
Chapter 9. Receptor Tyrosine Kinases in Cardiac Muscle
Overview of RTK Biology
RTK Expression and Function in Cardiac Myocytes
RTK Transactivation by GPCR
Conclusion: Toward Integrative Signaling Approaches
REFERENCES
Chapter 10. Communication in the Heart: Cardiokines as Mediators of a Molecular Social Network
Cardiokines and the Molecular Social Network of Cell Communication
Mechanisms of Secretory Protein Synthesis, Processing, and Secretion
ANP, The Archetype Cardiokine
Novel Autocrine and Paracrine Signaling Proteins in the Heart
Conclusions
Acknowledgments
REFERENCES
Chapter 11. Calcium Fluxes and Homeostasis
Introduction
Intracellular and Extracellular Ca2+ Concentrations During Diastole
Surface Membrane Ca2+ Efflux Mechanisms
Sarcoplasmic Reticulum (SR) Ca2+ Storage and Release
Mitochondrial Ca2+ Regulation
Ca2+, Mitochondria, Cell Death, and Contractile Dysfunction
Ca2+ and Transcriptional Regulation and Hypertrophy
Ca2+/CaM-CAMKII-HDAC Pathway
Ca2+-CaM-Calcineurin-NFAT Pathway
Ca2+ Flux Balance is Ca2+ Homeostasis
Physiological Regulation of Ca2+ to Control Cardiac Contractility
Dysregulated Ca2+ and Cardiac Dysfunction in Heart Disease
REFERENCES
Chapter 12. Excitation–Contraction Coupling in the Heart
Introduction
Excitation at the Sarcolemma
Ca2+ Release from the Sarcoplasmic Reticulum – Myocyte Contraction
Cardiomyocyte Relaxation
The RyR2 Macromolecular Complex and its Regulation
Regulation of EC Coupling by β-Adrenergic Stimulation
REFERENCES
Chapter 13. Role of Sarcomeres in Cellular Tension, Shortening, and Signaling in Cardiac Muscle
Introduction
Cardiac Sarcomeres Have Distinct Structures and Functions
State Changes in Cardiac Sarcomeres and the Heart Beat
Control of Contractility at the Level of Sarcomeric Proteins
Conclusions
Acknowledgments
REFERENCES
Chapter 14. Cardiovascular Mechanotransduction
Introduction
Acute Physiological Adaptations to Mechanical Stress
Overview and Localization of Mechanosensitive Structures
Mechanotransduction Initiated at the Sarcomere
Fibroblast–Cardiomyocyte Crosstalk
Conclusion
Acknowledgments
REFERENCES
Chapter 15. Cardiomyocyte Metabolism: All Is in Flux
Fuel Metabolism in Perspective
Mitochondria and the Dynamics of Metabolism in the Heart
The Highways of Energy Transfer
Tracing Metabolic Pathways ex vivo and in vivo
Genetic Models for the Elucidation of Cardiac Metabolism
Major Energy-Providing Substrates
Metabolic Remodeling
Conclusions
Acknowledgments
REFERENCES
Chapter 16. Transcriptional Control of Striated Muscle Mitochondrial Biogenesis and Function
General Overview of Mitochondrial Function and Biogenesis
Transcriptional Regulatory Circuitry Involved in Mitochondrial Biogenesis
Transcriptional Regulatory Circuitry Orchestrating Mitochondrial Biogenesis: The PGC-1 Coactivators
Defining the Requisite Role of Transcriptional Regulatory Factors in Striated Muscle Mitochondrial Biology and Physiology: Lessons from Gene-Targeted Mice
Implications for Myocardial Disease
Acknowledgments
REFERENCES
Chapter 17. Mitochondrial Morphology and Function
Relationships with Other Cellular Structures
Mitochondrial Compartments
Mitochondrial Shape and Tethering to the SR: Molecular Determinants
Energy-Linked Functions
Mitochondrial Generation of Reactive Oxygen Species
The Mitochondrial Permeability Transition Pore
Acknowledgments
REFERENCES
Chapter 18. Genetics and Genomics in Cardiovascular Gene Discovery
What is the Genetic Paradigm and Why is Genomics Indispensible?
The Structure and Conservation of the Human Genome
The Functions Encoded in the Human Genome
The Nature of Sequence Variation in Man: From Individual Genes to Whole Genomes
Mapping a Disease Locus by Linkage, Association, and Dosage Variants
Cardiovascular Genetics and Genomics: A Status Report Using Key Examples
REFERENCES
Chapter 19. Cardiovascular Proteomics: Assessment of Protein Post-Translational Modifications
Introduction
Technical Heart of Proteomics: Analytical Separation, Mass Spectrometry and Bioinformatics
Tackling the Subproteomes
Site-Specific Quantification of Protein PTMs by MRM
Conclusions
Acknowledgments
REFERENCES
Section B: Adaptations and Response
Chapter 20. Adaption and Responses: Myocardial Innervations and Neural Control
Introduction
Regulation of Brainstem Autonomic Function
Myocardial Innervations from Brainstem to Organ: Efferent Parasympathetic Innervation
Myocardial Innervations from Brainstem to Organ: Efferent Sympathetic Innervation
Myocardial Innervations: Cardiac Afferent Innervation
Integration of Sympatho-Vagal Balance at the Level of the Myocyte
Cardiac Autonomic Control and Cardiovascular Disease
REFERENCES
Chapter 21. Regulation of Cardiac Systolic Function and Contractility
Introduction: What is Contractility?
Measuring Systole
Control of Systole by Altered Loading
Control of Systole by Heart Rate
Post-Translational Regulation of Myofilament Proteins
Conclusion
REFERENCES
Chapter 22. Intracellular Signaling Pathways in Cardiac Remodeling
Concept of Physiological and Pathological Remodeling in Heart
Intracellular Signaling Pathways in Physiological Remodeling (Figure 22.2)
Intracellular Signaling Pathways in Pathological Remodeling
Conclusion
REFERENCES
Chapter 23. Oxidative Stress and Cardiac Muscle
Definition and Intracellular Dynamics of ROS
Physiological Function of ROS
The Role of Oxidative Stress in Mediating Cardiac Diseases and Aging
The Role of Reductive Stress in Mediating Cardiac Diseases
The Role of S-Nitrosylation and Nitrosative Stress in Mediating Cardiac Disease
Concluding Remarks
REFERENCES
Chapter 24. Physiologic and Molecular Responses of the Heart to Chronic Exercise
Physiologic Accommodations to Chronic Exercise
Can Physiologic Cardiac Adaptation Lead To Cardiac Pathology?
Molecular Remodeling in Physiologic Hypertrophy
Gene Expression
Myocardial Energetics and Mitochondrial Function
Nodal Signaling Pathways
Role of Non-Cardiocyte (Paracrine) Signaling Mechanisms
Future Directions/Therapeutic Targets
REFERENCES
Chapter 25. Epigenetics in Cardiovascular Biology
Introduction to Epigenetics
Epigenetics and Heart Development
Epigenetic Modifications in Cardiovascular Disease
Present and Future Prospects for Epigenetic Therapy in Cardiovascular Disease
REFERENCES
Chapter 26. Cardiac MicroRNAs
Introduction
MiRNA Biogenesis
miRNA Function in the Heart
MiRNA Dysregulation during Cardiac Disease
Therapeutic Regulation miRNAs
Plasma Detection of miRNAs as Novel Biomarkers for Cardiovascular Disease
Concluding Remarks
REFERENCES
Chapter 27. Protein Quality Control in Cardiomyocytes
Introduction
Chaperones in PQC
The Ubiquitin-Proteasome System
ER-Associated PQC and Cardiac Dysfunction
PQC Inadequacy in Cardiac Remodeling and Failure
REFERENCES
Chapter 28. Cardioprotection
Mechanisms of Muscle Injury and Cell Death
Cardioprotection Induced by Preconditioning and Postconditioning
Cardioprotective Agents and Strategies
Central Role of Mitochondria in Myocardial Cell Survival
Translation to the Clinic
Summary and Future Directions
REFERENCES
Chapter 29. Cardiac Fibrosis: Cellular and Molecular Determinants
Introduction
The Role of Cardiac Fibroblasts in the Myocardium
The Origin of Cardiac Fibroblasts
Development of Fibrosis
Clinical Manifestations of Cardiac Fibrosis
Treatment of Cardiac Fibrosis
Conclusion
REFERENCES
Chapter 30. Autophagy in Cardiac Physiology and Disease
Cardiac Growth and Plasticity
Autophagy: Cellular Cannibalization
Molecular Anatomy of Autophagy
Pathways Governing Autophagy
Functional Consequences of Autophagic Flux in the Heart
Autophagy in Human Cardiovascular Disease
Cardiac Autophagy as a Therapeutic Target
Summary and Perspective
Acknowledgments
REFERENCES
Chapter 31. Programmed Cardiomyocyte Death in Heart Disease
Introduction: The Role of Programmed Cell Death in Health and Disease
Different Mechanisms of Programmed Cell Death in the Heart
Programmed Cell Death in Heart Disease
Genetic and Pharmacological Inhibition of Programmed Cardiomyocyte Death
REFERENCES
Chapter 32. Wnt and Notch: Potent Regulators of Cardiomyocyte Specification, Proliferation, and Differentiation
Introduction
Cardiac Development: Contribution of Multiple Cell Lineages
Wnt Signaling in Cardiogenesis
Notch Signaling in Cardiogenesis
Conclusions
REFERENCES
Section C: Myocardial Disease
Chapter 33. Congenital Cardiomyopathies
Normal Muscle Structure and Function
Dilated Cardiomyopathy
Hypertrophic Cardiomyopathy
Restrictive Cardiomyopathy
Arrhythmogenic Cardiomyopathy
Left Ventricular Noncompaction
REFERENCES
Chapter 34. Genetics of Congenital Heart Disease
Introduction
T-Box Transcription Factors and Associated Factors: NKX2.5, GATA4, MYH6
Neural Crest Cells and Laterality: TFAP2B, CITED2, ZIC3
Cardiac Outflow Tract Development: Notch Signaling Pathway
Other Genetic Syndromes Caused by Single Gene Defects
REFERENCES
Chapter 35. Mechanisms of Stress-Induced Cardiac Hypertrophy
Introduction
Cardiac Hypertrophy
Biomechanical Stress Signaling and Cardiomyocyte Hypertrophy
Inhibition of Hypertrophy as a Therapeutic Concept
Conclusion
REFERENCES
Chapter 36. Ischemic Heart Disease
Introduction
Pathophysiology of Myocardial Ischemia
Myocardial Infarction
Chronic Ischemic Heart Disease
REFERENCES
Chapter 37. The Pathophysiology of Heart Failure
Introduction and Definitions
Symptoms of Heart Failure
Signs and Radiographic Features of Heart Failure
The Initial Deleterious Event
Neurohormonal Responses to the Initial Deleterious Event
Pathological Left Ventricular Remodeling
Hemodynamic Alterations in Heart Failure
Current Therapy of Heart Failure and Relationship to Pathophysiology
REFERENCES
Chapter 38. The Right Ventricle: Reemergence of the Forgotten Ventricle
Formation and Structure of the Right Ventricle
The Right Ventricle in Pulmonary Hypertension
Adaptive Versus Maladaptive RVH
Sympathetic Activation in PH
Right Ventricular Metabolism in RVH
Diseases of the Right Ventricle
Right Ventricular Infarction
Conclusion
REFERENCES
Chapter 39. Mammalian Myocardial Regeneration
Normal Myocardial Growth and Cell Cycle Activity
The Extent of Endogenous Myocardial Regeneration (Table 39.1)
Cardiac Progenitor Cells
Proliferation of Differentiated Cardiomyocytes
Conclusions
Acknowledgments
REFERENCES
Chapter 40. The Structural Basis of Arrhythmia
Introduction
Anatomy of the Cardiac Conduction System
Structural Basis for Bradyarrhythmias
Structural Basis of Tachyarrhythmias
REFERENCES
Chapter 41. Molecular and Cellular Mechanisms of Cardiac Arrhythmias
Brief Review of Cardiac Cellular and Tissue Electrophysiology
Abnormalities of Impulse Generation
Abnormalities of Impulse Propagation
Cardiac Remodeling
REFERENCES
Chapter 42. Genetic Mechanisms of Arrhythmia
Introduction
The Genetics of Mendelian Arrhythmogenic Disorders
Specific Molecular Mechanisms in Inherited Arrhythmias
REFERENCES
Chapter 43. Infiltrative and Protein Misfolding Myocardial Diseases
Introduction
Protein Misfolding in Cardiac Disease
Pathophysiology
Clinical Manifestations
Diagnosis
Myofibrillar Cardiomyopathies
Amyloid Cardiomyopathies
Therapy and Management
Future Directions
Acknowledgments
REFERENCES
Chapter 44. Cardiac Aging: From Humans to Molecules
Introduction
Macroscopic Structural and Functional Changes
Microscopic Structural and Functional Changes in Isolated Cardiac Muscle and Cell-Culture Systems
Conclusion
REFERENCES
Chapter 45. Adrenergic Receptor Polymorphisms in Heart Failure
Adrenergic Receptor Control of Ventricular Function
Relevance of Adrenergic Receptor Polymorphisms
Cardiac Function in Genetically Altered Mice
Human Studies
Conclusions
REFERENCES
Chapter 46. Cardiac Gene Therapy
Introduction
Gene Delivery
Targets
Clinical Trials
Conclusion
REFERENCES
Chapter 47. Protein Kinases in the Heart: Lessons Learned from Targeted Cancer Therapeutics
Introduction and Background
Her2/Erb-B2
Angiogenesis Inhibitors Targeting VEGF/VEGFRs and PDGFRs
PDGFR
Targeting The PI3-K Pathway
Applications of Kinase Inhibitors to Treat Cardiac Disease – The Other Side of the Coin
REFERENCES
Chapter 48. Cell Therapy for Cardiac Disease
Introduction
Potential Cell Sources
Mechanisms of Action for Cell-Based Therapies
Selected Cell Therapy Clinical Trials
Future Directions
REFERENCES
Chapter 49. Chemical Genetics of Cardiac Regeneration
Introduction
Small-Molecules and Stem Cells: Perfect Partners in an Imperfect World
In Vitro Biological Systems for Cardiac Differentiation
Physiological Screening
Ex Vivo Applications
Targeting The Niche In Vivo
Outlook
Acknowledgments
REFERENCES
Chapter 50. Device Therapy for Systolic Ventricular Failure
Introduction
Implantable Cardioverter-Defibrillators in Heart Failure
Ventricular Dyssynchrony and Heart Failure
Mechanically Assisted Heart Failure: Cellular and Molecular Observations on Reverse Remodeling
The Future: Bridging the Clinical Observations With the Current Understanding of Myocardial Reverse Remodeling
REFERENCES
Chapter 51. Novel Therapeutic Targets and Strategies against Myocardial Diseases
Introduction
G-CSF Therapy for Treatment of Myocardial Infarction
The Role of Tumor-Suppressor Gene Products in Myocardial Pathologies
REFERENCES
VOLUME 2
Part III: Skeletal Muscle
Section A: Basic Physiology
Chapter 52. Skeletal Muscle Development
Introduction
Trunk and Limb Muscles
Head Muscles
Acknowledgments
REFERENCES
Chapter 53. Skeletal Muscle: Architecture of Membrane Systems
The Membrane Systems Involved in Calcium Cycling
Mitochondria
Golgi and Associated Organelles
Pathology of Myofibrils and Membrane Systems
Acknowledgments
REFERENCES
Chapter 54. The Vertebrate Neuromuscular Junction
The Structure of the Junction
The Ultrastructure of the Junction
Clustering of AChR at the Synapse
A Modification to the Agrin Hypothesis: Muscle Pre-Patterning of Receptors
Retrograde Signaling
Structural Biology of the Nerve Terminal Via Electron Microscopy
The Life History of the Neuromuscular Junction
Specificity of Muscle Innervation
Muscle Plasticity Mediated by the NMJ
Some Issues in the Development of Motor Units
The Role of Synaptic Glia
Schwann Cells Play a Role in Repair of Muscle Innervation after Nerve Damage
Acknowledgments
REFERENCES
Chapter 55. Neuromechanical Interactions that Control Muscle Function and Adaptation
Impact of Motor Unit Organization on Muscle Function
Control of Muscle Fiber Diameter and Length
Integration of Active and Passive Elements of Neuromuscular Components, In Vivo
Links Between Neuromechanical and Molecular Mechanisms Underlying Muscle Protein Homeostasis
REFERENCES
Chapter 56. Control of Resting Ca Concentration in Skeletal Muscle
Introduction
Mechanisms for Ca2+ Removal from the Myoplasm of Muscle Cells
Mechanisms for Ca2+ Entry into the Myoplasm in Skeletal Muscle
Methods for Measurements Resting [Ca2+]I in Muscle Cells
Summary
Acknowledgments
REFERENCES
Chapter 57. Skeletal Muscle Excitation–Contraction Coupling
Overview of Steps in Skeletal Muscle Excitation–Contraction Coupling
The Muscle Fiber Action Potential Activates Force Production
A Rise in Myoplasmic [Ca2+] Links Fiber Depolarization to Force Activation
During Steady Experimental Depolarization, Maximum Force Increases Over a Narrow Voltage Range
Large Depolarizations Activate Force Within Milliseconds
Biophysical Characterization of the TT Voltage Sensors
Ca2+ Release Flux from the SR Exhibits an Early Peak and Rapid Inactivation During Depolarization
Molecular Components for T-Tubule Membrane Potential Control of SR Ca2+ Release
The Dihydropyridine Receptor is the Skeletal Muscle TT Voltage Sensor for EC Coupling
The Ryanodine Receptor is the SR Calcium Release Channel
SR Calcium Release Channels can be Studied Directly in Fragmented Systems, but Generally Lack the TT Voltage Sensor
Physiological Mechanism for Activation of the SR Calcium Release Channels in Muscle Fibers
Unitary Ca2+ Release Events: Ca2+ Sparks
Calcium Dependent Contractile Filament Activation
Relaxation
REFERENCES
Chapter 58. The Contractile Machinery of Skeletal Muscle
Sarcomeres are Repeating Units of the Myofibrils
Bands and Filaments
Thin Filament Regulation of Muscle Contraction
The Scaffolding Proteins Give Stability and Elasticity to the Sarcomere
The Z-Line is Involved in Signaling
Faults in the Cross-Striation Alignment
Z-Line Defects in Pathology
Acknowledgments
REFERENCES
Chapter 59. Skeletal Muscle Metabolism
Muscle Metabolism During the Absorptive State
Muscle Metabolism During Fasting
Muscle Metabolism During Exercise
Muscle Insulin Resistance
REFERENCES
Chapter 60. Skeletal Muscle Fiber Types
Diversity of Muscles, Motor Units, and Muscle Fiber Types
Muscle Fiber Types During Development and Aging
Molecular and Functional Differences Among Muscle Fiber Types
Signaling Pathways Involved in Fiber Type Specification and Remodeling
REFERENCES
Section B: Adaptations and Response
Chapter 61. Regulation of Skeletal Muscle Development and Function by microRNAs
microRNA Biogenesis and Function
Skeletal Muscle Without miRNAs
Skeletal Muscle-Specific miRNAs
miR-206 in Skeletal Muscle Function and Disease
miR-1 in Skeletal Muscle Development, Function and Disease
miR-133a in Skeletal Muscle Biology
MyomiRs and Myofiber Type Specification
Other miRNAs in Skeletal Muscle Biology
Therapeutic Implications of miRNAs in Skeletal Muscle Disorders
REFERENCES
Chapter 62. Musculoskeletal Tissue Injury and Repair: Role of Stem Cells, Their Differentiation, and Paracrine Effects
Pathophysiology of Skeletal Muscle Injury
Muscle Stem Cell-Mediated Skeletal Muscle Repair
Muscle Stem Cell-Mediated Cardiac Repair
Muscle Stem Cell-Mediated Bone Repair
Muscle Stem Cell-Mediated Cartilage Repair
Muscle Stem Cell Differentiation into Host Tissue is not a Major Determinant of Success of Repair
Conclusions
Future Directions in Stem Cell Therapy
Acknowledgments
REFERENCES
Chapter 63. Immunological Responses to Muscle Injury
General Characteristics of the Inflammatory Response to Acute Muscle Injury
The Th1 Inflammatory Response in Injured Skeletal Muscle
The Th2 Inflammatory Response in Injured Skeletal Muscle
Inflammatory Cell-Derived Cytokines Have Direct Effects on Muscle Growth and Regeneration
Future Directions
Acknowledgments
REFERENCES
Chapter 64. Skeletal Muscle Adaptation to Exercise
Specificity of Signaling
Adaptation of Skeletal Muscle to Resistance Exercise
Adaptation to Endurance Exercise
Future Directions
Acknowledgments
REFERENCES
Chapter 65. Skeletal Muscle Regeneration
Introduction
Requirement of Satellite Cells in Regeneration
Signaling Pathways in Skeletal Muscle Regeneration
Contribution to Muscle Regeneration by Other Stem Cells
Concluding Remarks
Acknowledgments
REFERENCES
Chapter 66. Skeletal Muscle Dystrophin-Glycoprotein Complex and Muscular Dystrophy
Introduction
The Dystrophin-Glycoprotein Complex in Skeletal Muscle
Dystroglycan: Post-Translational Processing and Function
Sarcoglycan-Sarcospan Subcomplex
Duchenne Muscular Dystrophy and Disruption of the Dystrophin-Glycoprotein Complex
Sarcoglycan-Deficient Limb-Girdle Muscular Dystrophy
Dystroglycanopathies: Limb-Girdle to Congenital Muscular Dystrophy
The Mechanistic Basis of Maintaining Muscle Membrane Integrity
REFERENCES
Section C: Skeletal Muscle Disease
Chapter 67. Statin-Induced Muscle Toxicity: Clinical and Genetic Determinants of Risk
Clinical Aspects
Pharmacokinetic Factors
Pharmacodynamic Factors
REFERENCES
Chapter 68. Myotonic Dystrophy
Genetics and Mechanism of Repeat Expansion
Skeletal Muscle in DM1
Skeletal Muscle in DM2
Cardiac Muscle in DM1
Cardiac Muscle in DM2
Pathophysiology of DM
Therapeutic Implications
REFERENCES
Chapter 69. Facioscapulohumeral Muscular Dystrophy: Unraveling the Mysteries of a Complex Epigenetic Disease
Clinical and Histological Features
Genetic Features
Epigenetic Features
Candidate Genes and Affected Pathways
Therapeutic Strategies
Outlook and Future Directions
Acknowledgments
REFERENCES
Chapter 70. ECM-Related Myopathies and Muscular Dystrophies
Introduction
Myopathies of the ECM
Disorders of the Reticular Lamina and Beyond
Other Skeletal Dysplasias
Summary
REFERENCES
Chapter 71. Molecular Pathogenesis of Skeletal Muscle Abnormalities in Marfan Syndrome
Introduction
Increased Activity of TGF-β Signaling in Marfan Syndrome
Functional Role of TGF-β Signaling in Skeletal Muscle
TGF-β Signaling in Skeletal Muscle of Marfan Syndrome (5)
REFERENCES
Chapter 72. Diseases of the Nucleoskeleton
Introduction
Structure and Function of the Nucleoskeleton
Diseases Linked to Defects of the Nucleoskeleton
Pathophysiological Mechanisms?
Conclusions and Perspectives
REFERENCES
Chapter 73. Channelopathies of Skeletal Muscle Excitability
Clinical Phenotypes from Channel Mutations that Alter Sarcolemmal Excitability
Chloride Channel Loss-of-Function Defects Cause Myotonia
Sodium Channel Gain-of-Function Mutations Cause Myotonia Or Periodic Paralysis
Leaky Mutant Sodium Channels Cause Hypokalemic Periodic Paralysis
Calcium Channel Mutations in Hypokalemic Periodic Paralysis
Inward Rectifier Potassium Channel Loss-of-Function Defects in the Andersen–Tawil Syndrome and Thyrotoxic Periodic Paralysis
REFERENCES
Chapter 74. Thick and Thin Filament Proteins: Acquired and Hereditary Sarcomeric Protein Diseases
Introduction
Altered Myosin and Actin Protein Expression
Hereditary Thick and Thin Filament Protein Myopathies
Acknowledgments
REFERENCES
Chapter 75. Metabolic and Mitochondrial Myopathies
Muscle Fat Metabolism and Disorders (Figure 75.1)
Muscle Carbohydrate Metabolism and Disorders (Figure 75.2)
Mitochondrial Myopathies
REFERENCES
Section D: Therapeutics
Chapter 76. Gene Therapy of Skeletal Muscle Disorders Using Viral Vectors
Introduction
Gene Therapy Vectors and Skeletal Muscle Transduction
Gene Therapy of the Muscular Dystrophies
Conclusions
Acknowledgments
REFERENCES
Chapter 77. Cell-Based Therapies in Skeletal Muscle Disease
Therapeutic Strategies for Muscular Dystrophies
Cell Candidates
Genetic Manipulation for Autologous Cell Therapy
Clinical Trials
Conclusion
Aknowledgments
REFERENCES
Chapter 78. Immunological Components of Genetically Inherited Muscular Dystrophies: Duchenne Muscular Dystrophy and Limb-Girdle Muscular Dystrophy Type 2B
Introduction
Duchenne Muscular Dystrophy
Limb-Girdle Muscular Dystrophy Type 2B
REFERENCES
Chapter 79. Myostatin: Regulation, Function, and Therapeutic Applications
Discovery of Myostatin and its Biological Function as a Negative Regulator of Muscle Mass
Regulation of MSTN Extracellularly by Binding Proteins
Development of MSTN Inhibitors as Potential Therapeutic Agents
Physiological Effects of Targeting MSTN Signaling in Normal and Disease Settings
Conclusions and Speculation
REFERENCES
Chapter 80. Insulin-Like Growth Factor I Regulation and Its Actions in Skeletal Muscle Growth and Repair
Introduction
IGF-I Activity and its Regulation
Regulation of IGF-I Production and Activity
Alternative Splicing
Potential Functions of IGF-I E-Peptides
IGF-I Processing
Targets for Therapy
Risks of IGF-I for Therapy
Current and Emerging Strategies for Therapy
REFERENCES
Chapter 81. Novel Targets and Approaches to Treating Skeletal Muscle Disease
Introduction
Disease Targets
Resealing Muscle Membrane Disruption
Stimulating Muscle Growth
Inflammation and Fibrosis
Calcium and Mitochondrial Dysregulation in Muscle Disease
Gene Correction Strategies
Conclusions
REFERENCES
Part IV: Smooth Muscle
Section A: Basic Physiology
Chapter 82. Development of the Smooth Muscle Cell Lineage
Diversity of the Smooth Muscle Cell Lineage(s)
SMC Progenitors and Stem Cells
Embryologic Origins of Smooth Muscle Cell Lineage
Conclusions and Future Directions
REFERENCES
Chapter 83. Smooth Muscle Myocyte Ultrastructure and Contractility
Introduction
The Contractile Apparatus
The Myosin Motor
Myosin Filaments
Contractile Regulation
Actin
Mechanics and Energetics of Contraction
Architecture and Function of the Sarcoplasmic Reticulum
Mitochondria
Surface Vesicles
Conclusion
Acknowledgments
REFERENCES
Chapter 84. Potassium, Sodium, and Chloride Channels in Smooth Muscle Cells
Introduction
Potassium Channels
Voltage-Sensitive Sodium Channels
Chloride Channels
Perspectives
REFERENCES
Chapter 85. G-Protein-Coupled Receptors in Smooth Muscle
Introduction
G-Protein-Coupled Receptors
G-Protein-Coupled Receptors Involved in the Regulation of Smooth Muscle Cell Function
Pharmacological Regulation of Smooth Muscle Function Through GPCRs
Conclusions
REFERENCES
Chapter 86. Calcium Homeostasis and Signaling in Smooth Muscle
Introduction
Sources of Ca2+ in Smooth Muscle Cells
Ca2+ Clearance Systems
Conclusion
REFERENCES
Chapter 87. Regulation of Smooth Muscle Contraction
Types of Contractile Stimulation
Contractile Signaling Pathways by Target
Organization of Signaling Pathways
Conclusions
REFERENCES
Section B: Heterogeneities
Chapter 88. Heterogeneity of Smooth Muscle
Introduction
Smooth Muscle
Smooth Muscle-Like Cells
Conclusion
Acknowledgments
REFERENCES
Chapter 89. Microcirculation
Introduction
Architecture of the Microcirculation
Arterioles and Arteriolar Smooth Muscle
Capillaries and Pericytes
Venules
Summary and Conclusions
Acknowledgments
REFERENCES
Chapter 90. Uterine Smooth Muscle
Excitation–Contraction Coupling in the Myometrium
Effects of Female Hormones on the Myometrium
Parturition
Conclusions
REFERENCES
Section C: Adaptations and Response
Chapter 91. Oxidative Stress, Endothelial Dysfunction, and Its Impact on Smooth Muscle Signaling
Introduction
The L-Arginine/No/cGMP Pathway in Vascular Tissue
Oxidative Stress and Endothelial Dysfunction
Endothelial Dysfunction and Cardiovascular Risk Factors
Vascular Superoxide Sources
Effects of Reactive Oxygen Species on the Activity and Expression of the sGC and the cGK-I
Oxidative Stress and Consequences for the Activity and Expression of the cGMP-Dependent Kinase I
Endothelial Function and Prognosis
Conclusion
REFERENCES
Chapter 92. Hemodynamic Control of Vascular Smooth Muscle Function
Introduction
Mechanical Forces in Vessel Physiology
Mechanosensitive Gene Expression Networks in VSMC
Mechanotransducers in VSMC
Recapitulation of Vascular Developmental Signaling
Conclusion
REFERENCES
Chapter 93. Myogenic Tone and Mechanotransduction
Myogenic Tone and Mechanotransduction
The Myogenic Response in Microcirculatory Control
The Underlying Mechanism(s)
Future Considerations
Acknowledgments
REFERENCES
Chapter 94. Cell–Cell Communication Through Gap Junctions
Coordination of Organ Function
Gap Junctions are Clusters of Intercellular Channels Formed by Connexins
Functional Aspects of Gap Junctional Coupling In Smooth Muscle In Specific Organs
Conclusion
REFERENCES
Chapter 95. Vascular Smooth Muscle Cell Phenotypic Adaptation
Normal Differentiated Phenotype of VSMC
Effectors of the Normal VSMC Differentiation Program
Conditions of VSMC Phenotypic Adaptation
Perspective
REFERENCES
Chapter 96. Molecular Pathways of Smooth Muscle Disease
Introduction
Migration
Proliferation
Inflammation
Conclusion
REFERENCES
Section D: Smooth Muscle Disease
Chapter 97. Genetic Variants in Smooth Muscle Contraction and Adhesion Genes Cause Thoracic Aortic Aneurysms and Dissections and Other Vascular Diseases
Introduction
Thoracic Aortic Aneurysms and Dissections
Mutations in Genes for SMC Contraction Proteins Cause Familial Thoracic Aortic Disease
Genetic Variants Contributing to Sporadic Thoracic Aortic Disease Disrupt Smooth Muscle Cell Contraction and Adhesion
ACTA2 Mutations Cause Occlusive Vascular Diseases in Addition to FTAAD
Syndrome of Global Smooth Muscle Dysfunction Due to a De Novo ACTA2 Mutation
Conclusion
REFERENCES
Chapter 98. Vascular Smooth Muscle Cell Remodeling in Atherosclerosis and Restenosis
Pathogenesis of Atherosclerosis and Vascular Remodeling
The Role of VSMC in Atheroma Evolution and Complications
Role of Adult Progenitor Cells in VSMC Remodeling During Atherosclerosis
Role of Genetics in VSMC Remodeling Leading to Atherosclerosis
Future Directions
REFERENCES
Chapter 99. Arterial Hypertension
Introduction
Vascular Smooth Muscle and Vascular Functional Changes in Hypertension
Vascular Smooth Muscle and Vascular Structural Changes in Hypertension
Molecular and Cellular Mechanisms of Vascular Remodeling
Vascular Smooth Muscle, Endothelial Function, and Hypertension-Associated Vascular Changes
Vascular Smooth Muscle, Inflammation, and Vascular Remodeling in Hypertension
Vascular Aging, Remodeling, and Hypertension
Vascular Calcification
Conclusions
Acknowledgments
REFERENCES
Chapter 100. Diabetic Vascular Disease
Introduction
Endothelial Dysfunction in Diabetes
The Role of Hyperglycemia in Endothelial Dysfunction
The Role of Hyperinsulinemia in Endothelial Dysfunction
The Role of the RAAS in Endothelial Dysfunction in Diabetes
The Role of Oxidative Stress in Diabetes-Related Endothelial Dysfunction
Conclusions
REFERENCES
Chapter 101. Vascular Mechanisms of Hypertension in the Pathophysiology of Preeclampsia
Preeclampsia
Placentation and the Origin of Preeclampsia
Placental Ischemia and Hypoxia
Endothelial Dysfunction in Preeclampsia
Potential Therapies for the Treatment of Preeclampsia
Conclusion
REFERENCES
Chapter 102. Erectile Dysfunction
Erectile Dysfunction is An Important Medical Condition
The Role of Smooth Muscle in Erectile Physiology
Maintenance of the Flaccid State
Initiation of An Erection
Biochemical Mechanisms Regulating Corporal Smooth Muscle Tone
The BK Channel Indirectly Blocks the L-Type Calcium Channel and is a Target For Treatment of Erectile Dysfunction
Calcium Sensitization of Smooth Muscle Cells
Regulation of Corporal Smooth Muscle Tone Through Changes in Myosin Isoform Expression
The Role of Androgens in Erectile Function
Mechanisms Underlying Priapism
Conclusion: Is it Easy to Treat Erectile Dysfunction?
REFERENCES
Chapter 103. Smooth Muscle in the Normal and Diseased Pulmonary Circulation
Introduction: Pulmonary Versus Systemic Circulations
Pulmonary Hypertension
Animal Models of Pulmonary Hypertension
Origins of Pulmonary Smc in Development and in Pulmonary Hypertensive Vascular Remodeling
Phenotypic and Functional Heterogeneity of PA-SMCs
Mechanisms Involved in Control of SMC (Or SM-Like Cell) Phenotype in Pulmonary Vascular Disease
Treatment of Pulmonary Hypertension
REFERENCES
Chapter 104. Airway Smooth Muscle and Asthma
Structure and Function of Airway Smooth Muscle
Excitation–Contraction Coupling and its Modulation in Asthma
Mechanical Adaptation of Airway Smooth Muscle
Molecular Mechanisms for Mechanical Adaptation of Airway Smooth Muscle
Regulation of Airway Smooth Muscle Function By Adhesion Complex Proteins
Summary and Conclusions
REFERENCES
Chapter 105. Aging
Introduction
Age-Related Modifications of Arterial Wall
Morphological and Functional Modifications of Aging SMCs
Modulation of Signaling Pathways in Aged SMC
Age-Related Accumulation of Advanced Glycosylation End Products in the Vessel Wall
Conclusions
REFERENCES
Chapter 106. Vascular Calcification
Clinical Significance
Clinical Interactions Between Vascular and Bone Therapies
REFERENCES
Chapter 107. Smooth Muscle Progenitor Cells: A Novel Target for the Treatment of Vascular Disease?
Introduction
The SPC Controversy
SPCs in Vascular Diseases
Molecular Mechanisms of Intimal SPC Accumulation
Therapeutic Options of Targeting SPCs
REFERENCES
Chapter 108. Smooth Muscle: Novel Targets and Therapeutic Approaches
Introduction
Novel Approaches to Therapeutic Targeting of Smooth Muscle Tissues
Summary and Conclusions
Acknowledgments
REFERENCES
Glossary
Index
Product Details
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Number. of pages: 1380
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Language: English
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Published: July 18, 2012
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Publisher: Elsevier/Academic Press
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Format: eBook, PDF file
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eBook ISBN: 9780123815118
About the Editors
Joseph Hill
Dr. Hill is a cardiologist-scientist whose research strives to decipher mechanisms of structural, functional, and electrical remodeling of the heart. He earned M.D. and Ph.D. degrees from Duke University, conducted postdoctoral scientific training with Jean-Pierre Changeux at the Institut Pasteur in Paris, and pursued clinical training in Internal Medicine and Cardiology at Brigham and Women’s Hospital, Harvard Medical School. Dr. Hill served on faculty at the University of Iowa for 5 years before moving in 2002 to UT Southwestern as Chief of Cardiology and Director of the Harry S. Moss Heart Center. Dr. Hill’s honors include election to the Association of University Cardiologists and the Association of American Physicians. Dr. Hill maintains an active clinical practice focusing on general cardiology, hypertension, and heart failure.Affiliations and expertiseProfessor of Internal Medicine and Molecular Biology; James T. Willerson, M.D. Distinguished Chair in Cardiovascular Diseases; Frank M. Ryburn, Jr., Chair in Heart Research, University of Texas Southwestern Medical Center, Dallas, TX, USA
Eric Olson
Dr. Olson has dedicated his career to deciphering mechanisms that control muscle gene regulation and development. He received B.A. and Ph.D. degrees from Wake Forest University. After postdoctoral training with Luis Glaser at Washington University School of Medicine, he joined the Department of Biochemistry and Molecular Biology at the M. D. Anderson Cancer Center in 1984 and became Professor and Chairman in 1991. In 1995, he founded the Department of Molecular Biology at UT Southwestern. Dr. Olson has received numerous prestigious awards and honors. He is a member of the American Academy of Arts and Sciences, and its Institute of Medicine.Affiliations and expertiseProfessor of Molecular Biology; Robert A. Welch Distinguished Chair; Annie and Willie Nelson Professor; Pogue Distinguished Chair in Research on Cardiac Birth Defects, University of Texas Southwestern Medical Center, Dallas, TX, USA
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