Post-Genomic Cardiology
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Post-Genomic Cardiology

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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 Jose Marin-Garcia, 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.
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Product details

  • Hardback | 944 pages
  • 220.98 x 279.4 x 45.72mm | 2,925.66g
  • Academic Press Inc
  • San Diego, United States
  • English
  • 2nd edition
  • 0124045995
  • 9780124045996
  • 1,763,796

Table of contents

Dedication
Preface
Section I: Post-Genomic Cardiology

Chapter 1. Introduction to the Molecular Biology of the Cell

Nucleic Acids, Genes, Chromatin, and Chromosomes
DNA Transacting Processes: Replication, Transcription, and Repair
Genetic Variability Associated with Human Diseases
Cell Cycle
References


Chapter 2. Methodologies in the Era of Cardiovascular "Omics"

Introduction
Genomics Approaches: NGS and GWAS
Transcriptomics
Proteomics and Interactomics
Metabolomics
Cardiac Imaging
Translational Bioinformatics
Conclusions
Summary
References


Chapter 3. Post-Genomics Cardiovascular Signaling Pathways

Introduction
Cardiac Signaling in Physiological Growth
Ca2+-Mediated Signaling
Signaling at the Plasma Membrane
Signaling at the Mitochondria
Cell-Cycle signaling, cell proliferation, and apoptosis
Stress, Survival, and Metabolic Signaling
Signaling in Cardiac Development and Aging
Conclusion
Summary
References




Section II: Pediatric Cardiology in the Post-Genomic Era

Chapter 4. Molecular Determinants of Cardiac Development

Introduction
Overview of Cardiac Morphogenesis
MicroRNAs in Cardiovascular Development
Conclusions
Summary
References


Chapter 5. Molecular Determinants of Congenital Heart Disease

Introduction
Etiology of CHD: Interplay of Genetic and Environmental Factors
Molecular Mechanisms of CHD
Syndromic CHDs Caused by Point Mutations
Nonsyndromic CHDs Caused by Point Mutations
Non-Syndromic CHD Caused by Impaired Signaling Pathways
Nonsyndromic CHD Caused by Point Mutations in Transcription Factors
Nonsyndromic CHDs Caused by Point Mutations in Structural Proteins
Noncoding RNAs and CHD
Conclusions
Summary
References




Section III: Post-Genomic Assessment of Coronary Artery Disease, Angiogenesis, and Hypertension

Chapter 6. Molecular Determinants of Atherosclerosis

Overview of Atherogenesis
Lipoproteins
Endothelial Dysfunction
Rho Kinases and Statins in Atherosclerosis
Tumor Necrosis Factor (TNF) in Atherogenesis
Monocytes and Macrophages
Antiinflammatory Factors
Conclusion
Summary
References


Chapter 7. Molecular Genetics of Coronary Artery Disease and Myocardial Infarction

Introduction
Animal Studies
Linkage and Genome-Wide Association Studies in Myocardial Ischemia
Candidate Gene Identification Approach
Genes and Inflammatory Signaling Pathways Involved in CAD/MI
Other Signaling Pathways in CAD/MI
Additional Gene LOCI Associated with MI
Sex Hormone and MI
Gene Profiling in Myocardial Ischemia/Infarct
Genetics and Ethnic Differences in Coronary Artery Disease
Beyond GWAS
MicroRNAs Markers in CAD/MI
Conclusions
Summary
References


Chapter 8. Cellular and Molecular Aspects of Cardioprotection

Introduction
Cellular and Molecular Events in IPC
IPC and Potassium Channels
Signaling Pathways
Cell Death
Early and Late IPC Pathways
IPC and Cell Death
Mitochondrial Activity and ATP Levels in IPC
Mitochondria and Antioxidants
Gene Expression in Early IPC (Signaling Book)
Postconditioning and Cardioprotection
Remote Conditioning
Application in Humans
microRNAs in Cardioprotection
Conclusions and Future Perspective
Summary
References


Chapter 9. Molecular Determinants of Cardiac Neovascularization

Introduction
Vasculogenesis
Angiogenesis
Arteriogenesis
Molecular Mechanisms of Neovascularization
Therapy
Conclusions and Future Perspectives
Summary
References


Chapter 10. Post-Genomics Appraisal of Systemic and Pulmonary Hypertension

Introduction
Animal Models of Hypertension
Gene Expression and Profiling in Primary Systemic Hypertension
Genetics of PPH
Conclusions and Future Directions
Summary
References




Section IV: Post-Genomic Analysis of the Myocardium

Chapter 11. Post-Genomic Appraisal of Myocarditis

Introduction
Pathogenesis of Autoimmune Myocarditis
Signaling Pathways of Innate and Acquired Immunity
Treatment
Conclusions
Summary
References


Chapter 12. Cardiomyopathies: A Comparative Analysis of Phenotypes and Genotypes

Introduction
Hypertrophic Cardiomyopathy
Genetics of HCM
Animal Models of Genetic HCM
Dilated Cardiomyopathy
Transgenic Models of Dilated Cardiomyopathy
Mechanistic Hypotheses of DCM
Restrictive Cardiomyopathy
Arrhythmogenic Right Ventricular Dysplasia
Unclassified Cardiomyopathies
Cardiomyopathy and Diabetes Mellitus
Genetics in Diabetes
Conclusion
Summary
References




Section V: Heart Failure, Cell Death, and Mitochondria Dynamics

Chapter 13. Gene Profiling, Energy Metabolism, and Remodeling of the Failing Heart

Introduction
The Profiling of Gene Expression in Heart Failure
Global and Specific Analysis of Gene Expression
Epigenetics and HF
Histone/Chromatin Modifications; Epigenetic Control of Gene Expression
DNA modification/methylation
Transcriptional Coactivator p300 and Cardiac Hypertrophy
Energy Metabolism Profiling
Intracellular Calcium-Cycling Profiling
The Genetics of Human HF
Bioenergetics and Metabolic Changes in the Failing Heart
Mitochondrial DNA Integrity and HF in Transgenic Mice
Peroxisome proliferator activated receptor gamma coactivator 1 (PGC1)
Peroxisome Proliferator Activated Receptor (PPAR)
Mitochondrial Gene Profiling
Implication of Metabolic Genes in HF
From Cardiac Remodeling to Overt HF
Conclusion
Summary
References


Chapter 14. Oxidative Stress and Cell Death in Cardiovascular Disease: A Post-Genomic Appraisal

Introduction
Oxidative Stress
Cell Death
Conclusions
Summary
References


Chapter 15. The Emerging Role of Mitochondrial Dynamics in Cardiovascular Disease

Introduction
Mechanisms of Mitochondrial Fusion and Fission
Physiological Roles of Mitochondrial Dynamics
Mitochondrial Dynamics in the Normal and Diseased Heart
Conclusions
Summary
References




Section VI: Molecular and Genetic Analysis of Metabolic Disorders

Chapter 16. Post-Genomic Analysis of Fatty Acid and Glucose Metabolism in Cardiovascular Disease

Introduction
Metabolism of Fatty Acids and Glucose in Normal Cardiomyocytes
Regulatory Elements of Cardiac Bioenergy Molecules Metabolism
Metabolic Dysfunction and Cardiovascular Disease Phenotypes
Metabolic Therapies: Current Status and Perspectives
Summary
References




Section VII: Molecular Genetics of Dysrhythmias

Chapter 17. Post-Genomic Analysis of Dysrhythmias and Sudden Death

Introduction
Etiology of Cardiac Dysrhythmias
Ventricular Action Potential and Ion Currents
Cardiac Ion Channels
Properties of Ion Channels
Inherited Cardiac Dysrhythmias
Acquired Dysrhythmias
Mitochondria and Heart Rhythm Disorders
Animals Models for Cardiac Dysrhythmias
Post-Genomic Approaches to Rhythm Disorders
Conclusions and Future Prospects
Summary
References




Section VIII: Genes, Gender, and Epigenetics

Chapter 18. Gender and Cardiovascular Disease in the Post-Genomic Era

Introduction
Sex Steroid Hormones
Role of Gonadal Hormones in Cardiac Pathology
Animal and In Vitro Studies
Studies in Humans
Gender-Related Gene Regulation and Cardiovascular Disease
Epigenetic and Environmental Factors of Sex-Related Specifics of Cardiovascular Disease
Conclusion
Summary
References




Section IX: Aging and the Cardiovascular System

Chapter 19. The Aging Heart: A Post-Genomic Appraisal

Introduction
Telomere Analysis
Telomeres and CV Aging
Signaling Pathways in the Aging Heart
Signaling in the Endothelium in Aging
Cellular Damage/Cell Loss, Mitochondria, and CV Aging
Reactive Oxidative Species Generation and Aging in the Heart
Inflammation and CV Aging
Neurohormonal Signaling in CV Aging
Prodeath and Prosurvival Signaling Pathways in Aging
Signaling Factors in Cell Regeneration of the Aging Heart
Genetic Makeup of the Aging Heart
Epigenetic and Environmental Factors in Cardiac Aging
Gene Transfer in Cardiovascular Tissue
Knockout Transgenic Animal Models of Aging
Gene Profiling: Transcriptome and Proteomic Analysis
Proteomic Analysis
DNA Damage and Mutations in Aging
Conclusion
Summary
References


Chapter 20. Targeted Strategies to Fight Cardiac Aging

Introduction
Attenuating Cell Death and Remodeling
Initiating Prosurvival Pathways
Removing "Biological Garbage" in Aging: Targeting Lysosomes, Proteasomes and Other Approaches to Enhance Catabolic Gain
Genomic Instability
Conclusion
Summary
References


Chapter 21. Aging and the Cardiovascular System: The Road Ahead

Introduction
Genetic Analysis in Aging Research
Advances in Human Genotyping and Human Gene Analysis
Search for Biomarkers of Human Aging
Reversing Aging and/or Dysfunction of Age-Associated Diseases
Targeting Specific Organelles in Aging: Mitochondria/Lysosome
Diastolic Dysfunction in Aging
Pharmacogenomics and Nutrigenomics
Conclusions and Future Perspective
Summary
References




Section X: Genetics, Epigenetics, and New Approaches to Treatment

Chapter 22. Epigenetics and Cardiovascular Disease

Introduction
Basic Epigenetic Mechanisms
Cardiovascular Epigenetics
Conclusions
Summary
References


Chapter 23. Gene- and Cell-Based Therapy for Cardiovascular Disease

Introduction
Gene Therapy
Potential Molecular Targets
MicroRNA Therapeutics for CVD
Cell-Based Therapy
Cell Sources
Cardiac Progenitor Cells
Epicardial Progenitor Cells
Strategies for Cell Purification, Delivery, and Engrafting
Mechanisms of Heart Regeneration
Empowering Human Heart Regeneration
Conclusions
Summary
References




Section XI: Looking to the Future

Chapter 24. The Path to Personalized Cardiovascular Medicine

Introduction
Genomic and Epigenomic Analysis
Transcriptomics
Proteomics and Metabolomics
Cardiovascular Pharmacogenetics and Pharmacogenomics
Integrating "Omics": Systems Biology and Network Medicine
Conclusions
Summary
References




Glossary
Index
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Review Text

"This Second edition of Post-Genomic Cardiology (PCG) deals with what promises to be the cardiology of the future. As the role of genetic screening in cardiology is strengthened, and as research on the multiple signaling pathways involved in cardiac organogenesis and pathology progresses, this 2nd edition of PCG further attempts to integrate known facts with what is still developing and with what is slowly becoming known. New areas of interest to cardiologists and researchers include systems biology, the constructive cycle of computational model building, and experimental verification. These are capable of providing the input necessary for exciting new discoveries, including the management of diseases in a "personalized way. The book is fascinating because it introduces a field that no one with a minimum amount of scientific interest will be able to avoid in the very near future. Extensively referenced, and thoroughly researched, this book presents well-written and organized chapters, each with a summary of the important points discussed, followed by exhaustive bibliographies. A detailed glossary clearly defines the many acronyms used throughout the book. Unquestionably, this volume will be of great interest and use to clinical and research cardiologists, pharmacologists and genetics investigators; and to students of basic sciences. Dr. Marin-Garcia - author and editor of this 2nd edition of PGC has done an outstanding job of completing this challenging task." --Dr. Daniel Shindler

"This is a great book." --Dr. A. Bayes de Luna

"Seven years ago, I was given the opportunity to review the first edition of this book, which was published in 2007. Dr. José Marín-García has updated and revised a new edition of that work. In these 7 years, we have been witnesses to the great surge in research into the genetic and molecular bases of cardiovascular disease. The use of ''omics'' has contributed enormously to this advance in the existing knowledge. The study of the genetic bases of diseases, building on linkage studies, genome-wide association studies, and genome sequencing (genomics), together with the new methods for studying gene expression (transcriptomics) and its regulation (epigenomics), advances in the quantification of proteins (proteo- mics) and their metabolites (metabolomics), the study of the molecular mechanisms that take place within the cell, such as signaling pathways and cascades, cell reprogramming, and the integration of all this information through the systems biology and the bioinformatics, have contributed to these advances. In this book, the author presents an ambitious review of all these aspects, focusing not only on genomic aspects, but on post-genomic aspects and their contribution to the current knowledge of the molecular bases of heart disease as well.

As I mentioned in my review of the earlier edition, the fact that the book was written by a single author, with the participation of three close associates, lends consistency and uniformity to the different chapters and facilitates their reading. Each chapter finishes with a highly useful summary that presents the main conclusions and the most important messages. The majority of the chapters provides a very extensive list of references (updated as of 2012), which facilitates the consultation of the original sources of the information. There are many tables summarizing the data and, in this new edition, the quality of the figures and graphs has improved quite notably.

The current edition has 11 well differentiated sections, each of which is divided into several chapters (between 1 and 5) that deal with different aspects related to the genomics of heart disease. With respect to the earlier edition, the contents have been updated and include new sections or chapters that are mainly related to the relevance of epigenetics and the mitochondrion to heart disease.

Section I offers a general introduction to the biochemical, cellular, and molecular fu
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Review quote

"This Second edition of Post-Genomic Cardiology (PCG) deals with what promises to be the cardiology of the future. As the role of genetic screening in cardiology is strengthened, and as research on the multiple signaling pathways involved in cardiac organogenesis and pathology progresses, this 2nd edition of PCG further attempts to integrate known facts with what is still developing and with what is slowly becoming known. New areas of interest to cardiologists and researchers include systems biology, the constructive cycle of computational model building, and experimental verification. These are capable of providing the input necessary for exciting new discoveries, including the management of diseases in a "personalized" way. The book is fascinating because it introduces a field that no one with a minimum amount of scientific interest will be able to avoid in the very near future. Extensively referenced, and thoroughly researched, this book presents well-written and organized chapters, each with a summary of the important points discussed, followed by exhaustive bibliographies. A detailed glossary clearly defines the many acronyms used throughout the book. Unquestionably, this volume will be of great interest and use to clinical and research cardiologists, pharmacologists and genetics investigators; and to students of basic sciences. Dr. Marin-Garcia - author and editor of this 2nd edition of PGC has done an outstanding job of completing this challenging task." --Dr. Daniel Shindler

"This is a great book." --Dr. A. Bayes de Luna

"Seven years ago, I was given the opportunity to review the first edition of this book, which was published in 2007. Dr. Jose Marin-Garcia has updated and revised a new edition of that work. In these 7 years, we have been witnesses to the great surge in research into the genetic and molecular bases of cardiovascular disease. The use of ``omics'' has contributed enormously to this advance in the existing knowledge. The study of the genetic bases of diseases, building on linkage studies, genome-wide association studies, and genome sequencing (genomics), together with the new methods for studying gene expression (transcriptomics) and its regulation (epigenomics), advances in the quantification of proteins (proteo- mics) and their metabolites (metabolomics), the study of the molecular mechanisms that take place within the cell, such as signaling pathways and cascades, cell reprogramming, and the integration of all this information through the systems biology and the bioinformatics, have contributed to these advances. In this book, the author presents an ambitious review of all these aspects, focusing not only on genomic aspects, but on post-genomic aspects and their contribution to the current knowledge of the molecular bases of heart disease as well.

As I mentioned in my review of the earlier edition, the fact that the book was written by a single author, with the participation of three close associates, lends consistency and uniformity to the different chapters and facilitates their reading. Each chapter finishes with a highly useful summary that presents the main conclusions and the most important messages. The majority of the chapters provides a very extensive list of references (updated as of 2012), which facilitates the consultation of the original sources of the information. There are many tables summarizing the data and, in this new edition, the quality of the figures and graphs has improved quite notably.

The current edition has 11 well differentiated sections, each of which is divided into several chapters (between 1 and 5) that deal with different aspects related to the genomics of heart disease. With respect to the earlier edition, the contents have been updated and include new sections or chapters that are mainly related to the relevance of epigenetics and the mitochondrion to heart disease.

Section I offers a general introduction to the biochemical, cellular, and molecular functions of the heart under normal conditions. This section includes 3 chapters, the first 2 of which have been extensively rewritten. The 3 chapters introduce and review basic concepts related to gene structure, the processes of transcription and protein synthesis, and the cell cycle. The second chapter presents the methods for studying cardiac function at the molecular level, focusing on the different ``omics''. The last chapter of the section provides a review of the cell signaling pathways that regulate the growth, proliferation, and function of different cardiac cell lines. The author has updated the review of cell receptors and mitochondrial signaling, but the review of the intracellular pathways (adenyl cyclase, phospholipase, mitogen-activated protein [MAP] kinase, protein kinase, etc.), calcium signaling, and signals for cell cycle regulation, proliferation, and apoptosis has not been updated to any great extent in this second edition.

In section II, which is completely new, the author presents an excellent review, in 2 chapters, of the molecular mechanisms involved in embryonic heart development. In the first, he reviews the different signaling pathways and certain epigenetic factors that influence and regulate cell reprogramming in normal heart development; the second describes the known molecular changes that explain different congenital heart diseases.

Section III is the most extensive, with 5 chapters devoted to the analysis of arteriosclerosis, ischemic heart disease, angiogenesis, and hypertension. The first chapter describes the molecular mechanisms of arteriosclerosis and the second, the genetic bases of ischemic heart disease. In this second chapter, considerable weight is still given to evidence (often debatable) from linkage studies in family groups and from studies based on candidate genes. .....

Sections IV and V have also been extensively updated and restructured, and focus on the study of myocarditis, cardiomyopa- thies, and heart failure. They describe the genes and signaling pathways involved in cardiomyopathies (hypertrophic, idiopathic dilated, and restrictive cardiomyopathy and arrhythmogenic right ventricular dysplasia), in the cardiac response to inflammation and infection, and in the development of heart failure in patients with ischemic heart disease or hypertension. In this respect, the author has updated the content concerning ventricular remodeling, apoptosis and oxidative stress, and mitochondrial function in heart failure.

The book also reviews the molecular bases of arrhythmias, describing the genes involved in different channelopathies and in atrial fibrillation. The author presents and describes certain mutations than can be associated with a poorer prognosis in several heart diseases, although he admits that there are still many gaps in the current knowledge and, thus, cannot support their systematic utilization, and considers it necessary to continue to investigate the molecular mechanisms that regulate the different clinical presentations of a given genetic mutation.

Section VIII has only 1 chapter, which analyzes aspects related to sex differences in the context of cardiovascular diseases.

The last 3 sections are very new and provide an exhaustive presentation of aspects related to the aging of the heart and cardiovascular system (3 chapters), the epigenetic mechanisms related to cardiovascular diseases, and possible new therapeutic horizons that all this knowledge is opening along the path toward personalized cardiovascular medicine.

In conclusion, as I commented with regard to the previous edition, this is a highly interesting book that focuses on molecular mechanisms related to different heart diseases, which undoubtedly can be of great utility to cardiologists and researchers in different areas (pharmacology, basic research, clinical practice, epidemiology) who are interested in these mechanisms." --Roberto Elosua, Epidemiologia y Genetica Cardiovascular, Instituto Hospital del Mar de Investigaciones Medicas, Barcelona, Spain
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About José Marín-García

Dr.Jose Marin-Garcia, highly respected cardiologist, is the current Director of Molecular Cardiology and Neuromuscular Institute in Highland Park, NJ. He has 189 listed publications and an H-index of 30. He has written and edited Mitochondria and the heart (2005), Aging and the Heart (2008), Signaling in the Heart (2008). Heart Failure (2010), Post-Genomic Cardiology (2007), and Mitochondria and Their Role in Cardiovascular Disease (2012).
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