Cardiovascular Proteomics Techniques

Cristina Banfi, PhD has been leading the Laboratory of Functional Proteomics, Metabolomics and Network Analysis at Cardiologic Monzino Center in Milan since 2005. She has served as the Coordinator of Target Discovery Area since 2020 and is Adjunct Professor of Biomedical Omics at the University of Milan. Dr. Banfi is a leading authority in the field of proteomics, having published more than 200 peer-reviewed papers and book chapters. Additionally, she acts as a reviewer for several prominent journals.

• List of Contributors xviiPreface xxiii1 Basic Concepts in Mass Spectrometry 1Pietro Traldi and Gianluca Bartolucci1.1 Introduction 11.2 Mass and Energy 21.3 Mass Spectrometry-Based Proteomic Analyses 41.4 Mass Spectrometry in Quantitative Protein/Peptide Analyses 231.5 Posttranslational Modifications Investigated by Mass Spectrometry 271.6 Outlook and Conclusion 28References 282 Overview of Antibody-Based Technologies for Multiplexed Protein Detection and Quantification and Their Complementarity to Mass Spectrometry-Based Protein Profiling 31Sonia Eligini, Erica Gianazza, and Alice Mallia2.1 Introduction 312.2 Clinical Potentials of Mass Spectrometry-Based Proteomics 312.3 Mass Spectrometry-Based Proteomic Analysis Workflow: from Biomarker Discovery to Validation 322.4 Proteomic Analysis of Biological Samples: from Sample Preparation to Proteome Characterization for the Identification of Disease or Drug Candidates 342.5 Applications of the Emerging Mass Spectrometry-independent Targeted Proteomic Technologies in the Cardiovascular Field 422.6 Conclusions 57References 583 General Features of the Cardiovascular System 65Paul A. Iaizzo3.1 Introduction 653.2 Components of the Cardiovascular System 653.3 Summary 77References and Resources 774 Albumin and Cardiovascular Diseases 79Cristina Banfi4.1 Introduction 794.1.1 Structure and Functions of Human Albumin 794.2 Conclusion 98References 995 Platelets: From Biomarker Discovery to Drug Target Identification by Proteomics 107Cristina Banfi5.1 Platelet Biology 1075.2 Platelet Activation and Signaling 1085.3 Platelets in Diseases 1125.4 Role of Proteomics in Platelet Study 1155.5 Post-translational Modifications of Platelet Proteins 1245.6 Conclusions 130References 1316 The Role of Proteomics in Extracellular Vesicles Research in Cardiovascular Disease 139Maísa García-Arguinzonis and Lina Badimon6.1 History of EVs 1396.2 Classification of EVs 1406.3 Biogenesis of EVs 1406.3.1 Exosomes 1406.3.2 Microvesicles 1416.3.3 Apoptotic Bodies 1436.4 Other Extracellular Particles 1436.5 Source of EVs in Cardiovascular Disease Studies 1446.6 EV Isolation from Cell Cultures 1446.7 Collection of EVs from Blood 1446.8 Urine-EVs Separation 1466.9 EVs from Solid Tissue 1466.10 Storage of EVs 1466.11 Isolation and Purification Methods 1476.12 EV Separation Methods 1476.13 Characterization of EVs 1506.14 Proteomics 1516.15 EVs in Cardiovascular Diseases 1556.16 EVs in Atherosclerosis 1556.17 EVs in Myocardial Infarction 1576.18 EVs in Angiogenesis 1596.19 EVs in Heart Failure 1606.20 Engineered EVs 1616.21 EV Databases 1626.22 Conclusion 163References 1637 Proteomics of Human Lipoproteins in Cardiovascular Diseases 177Cristina Banfi7.1 Introduction 1777.2 Chylomicrons Biogenesis and Metabolism 1787.3 Very Low-Density Lipoprotein 1837.4 Low-Density Lipoprotein 1897.5 Lipoprotein(a) 1937.6 High-Density Lipoprotein 1967.7 Methodological Approaches for Isolating Lipoproteins 2007.8 Multiplexing Analysis of Apolipoproteins in the Human Blood 2027.9 Conclusions 203References 2048 Extracellular Matrix in Cardiovascular Pathophysiology: Proteomic Insights and Advancements to Mass Spectrometry-Based Characterization 215Rachel Cahalane, Mandy E. Turner, Elena Aikawa, and Cassandra L. Clift8.1 An Introduction to the Extracellular Matrix 2158.2 Extracellular Matrix in Cardiovascular Pathobiology 2198.3 Proteomic Targeting of the ECM 2338.4 Conclusions and Future Directions 235References 2369 Pathogenesis of Atherosclerosis: What We are Learning from Proteomics 255David del Rio-Aledo, Estefanía Núñez, Emilio Camafeita, Isabel Cerro-Pardo, Rafael Barrero, Ana Martínez del Val, Consuelo Marín, Luis Miguel Blanco-Colio, Jesús Vázquez, and Jose L. Martin-Ventura9.1 Introduction 2559.2 Fundamentals of Proteomics in Atherosclerosis 2559.3 Mechanisms Involved in Atherosclerotic Plaque Development and Progression 2609.4 Proteomic Biomarkers in Atherosclerosis 2689.5 Future Perspectives and Challenges in Atherosclerosis Proteomics 2709.6 Concluding Remarks 273References 27310 Emerging Insights into the Pathobiology of Acute Coronary Syndromes 283Gabriele Nieddu, Marilena Formato, and Antonio J. Lepedda10.1 Introduction 28310.2 Searching for Circulating Biomarkers of ACS by Applying MS-based Technologies 28910.3 Atherosclerotic Plaque Dissection through Proteomics 29910.4 Conclusions 302References 30311 Valvular Heart Disease, from Physiopathology to Biomarker Discovery 313Sasha A. Singh and Elena Aikawa11.1 Introduction 31311.2 Physiopathology of Valvular Heart Disease, a Historical Perspective 314References 33312 Pathophysiology of Heart Failure 341Giorgia Panichella and Alberto Aimo12.1 Introduction 34112.2 Hemodynamic and Structural Changes 34212.3 Neurohormonal Dysregulation 34412.4 Cellular and Molecular Mechanisms 35112.5 Comorbidities and Multisystem Involvement 35412.6 Right Ventricle in Heart Failure 35512.7 Genetic Contributions to Heart Failure 35612.8 Heart Failure as a Continuum Spectrum 35712.9 Heart Failure with Preserved Ejection Fraction 35812.10 The Contribution of Proteomics in Heart Failure 36012.11 Conclusions 362References 36213 Diseases of the Aorta, Recent Insights 371Raghav Gupta, Ashley Dinh, Sarah J. Parker, and Elizabeth L. Chou13.1 Introduction 37113.2 Epidemiology of Aortic Aneurysm and Dissection 37213.3 Aortic Physiology 37313.4 Investigation of Aortic Aneurysms and Dissections 37413.5 Summary of Genes Linked to Aortic Aneurysm and Dissection 37513.6 The Omics of Ascending Thoracic Aortic Aneurysm and Dissection 37813.7 The Unique Value of Proteomics for Hereditary Aneurysm Research 37913.8 Application of Proteomics to Aortic Aneurysms and Dissections 38013.9 Beyond Bulk Proteomics for Mechanistic Discovery in Aortic Aneurysms and Dissections 38113.10 Conclusion 385References 38514 Unveiling Sex and Gender Differences in Cardiovascular Diseases 391Daniela Trabattoni, Giovanni Teruzzi, Giuseppe Calligaris, and Sebastiano Gili14.1 Introduction 39114.2 Sex-Related Differences in Clinical Presentation, Risk Factors, and Diagnostic Evaluation of CAD 39114.3 Primary Prevention 39214.4 Detection of Coronary Artery Disease 39414.4.9 Mechanical and Emotional Stressors 40014.5 Acute Coronary Syndromes in Obstructive Coronary Disease 40714.6 Gender Differences in PCI Outcomes 40714.7 The Role of Coronary Imaging in Imaging 40914.8 Psychological Issues in Gender Cardiovascular Medicine 41314.9 Pathophysiology Basis of Non-Atherosclerotic Coronary Disease in Women 41614.10 The Contribution of Proteomics in Unveiling Sex and Gender Differences 417References 41915 Trends in Mass Spectrometry Imaging for Cardiovascular Diseases 431Johs Dannesboe and Berta Cillero-Pastor15.1 Introduction 43115.2 Definition and Basic Principles of Mass Spectrometry Imaging 43115.3 Brief History of Mass Spectrometry Imaging in Biomedical Research 43215.4 Importance of Mass Spectrometry Imaging in Cardiovascular Disease Research 43315.5 Basic Principles and Workflow 43315.6 Small Molecule and Lipid Imaging in Cardiovascular Research 44015.7 Challenges and Limitations 442References 44416 Network Medicine: A New Paradigm for Cardiovascular Disease Research and Beyond 449Niv Vigder, Stuart J. Cordwell, and Joseph Loscalzo16.1 Introduction to Network Medicine 44916.2 Introduction to Network Science and Biological Networks 45016.3 Progress Toward Reference Organismal Interactomes 45916.4 Complex Diseases Manifest as Nodal and Edgetic Perturbations 46416.5 Expanding the Interactome to Incorporate Complex Biological Phenomena 46616.6 Context-Specific Interactomes Resolve Complex Biological Heterogeneity 46816.7 Network Approaches Reveal Novel Disease Genes and Gene Products 47116.8 (Re)defining Relationships Between Diseases Using Network Medicine 47216.9 Network Approaches to Disease Reappraisal and Patient Subgrouping 47316.10 Network Approaches to Disease Pharmacology 47616.11 Conclusions 478References 47917 Recent Advances in Cardiovascular Plasma Proteomics 487Nicolai B. Palstrøm, Amanda J. Campbell, and Hans C. Beck17.1 Introduction 48717.2 Clinical Plasma Proteomics 48817.3 The Proteomics Toolbox: Analytical Methods in Cardiovascular Clinical Plasma Proteomics 49117.4 Application of Plasma Proteomics in Cardiovascular Research 50017.5 Challenges Regarding the Translation of Proteomics into the Clinic 50417.6 Recent Advances within Cardiovascular Plasma Proteomics 50717.7 Outlook 509References 51018 Unexplored Cardiac Diseases: Takotsubo Syndrome 523Liam S. Couch18.1 Introduction 52318.2 Clinical Presentation 52318.3 Multifactorial Pathophysiology of Takotsubo Syndrome 52418.4 The Role of Catecholamine Signaling 52518.5 Cardiomyocyte Calcium Handling 52718.6 Deranged Cardiomyocyte Metabolism 52718.7 Myocardial Inflammation and Edema 52818.8 Estrogen Withdrawal Post-menopause 52918.9 Altered Coronary Blood Flow 52918.10 Genomic Associations 53118.11 Brain Heart Interaction 53118.12 Scope for Future Utilization of Proteomics 532References 532Index 541