Post-Genomic Cardiology - 2nd Edition - ISBN: 9780124045996, 9780124046429

Post-Genomic Cardiology

2nd Edition

Authors: José Marín-García
Hardcover ISBN: 9780124045996
eBook ISBN: 9780124046429
Imprint: Academic Press
Published Date: 4th June 2014
Page Count: 944
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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.

Key Features

  • 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


Cardiologists, geneticists, physiologists, cell and developmental biologists as well as clinicians with interests in metabolic disease, neonatal medicine and aging specialists.

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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About the Author

José Marín-García

Dr.José Marín-García, 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).

Affiliations and Expertise

Director, The Molecular Cardiology and Neuromuscular Institute, Highland Park, NJ, USA


"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 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, Epidemiologıa y Genetica Cardiovascular, Instituto Hospital del Mar de Investigaciones Medicas, Barcelona, Spain