The Vasculome

From Many, One

1st Edition - June 11, 2022
Editor: Zorina S. Galis
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 2 2 5 4 6 - 2
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 2 5 4 7 - 9

The Vasculome: From Many, One introduces the fundamental bases of the “unity in diversity” of the Vasculome, from the coming together of various cell lineages during developme… Read more

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The Vasculome: From Many, One introduces the fundamental bases of the “unity in diversity” of the Vasculome, from the coming together of various cell lineages during development, to its deceptively simple solution for architectural design: the efficient interplay of a few types of building blocks supporting key similar functions throughout the body and their highly specialized functional local variations. Specific examples are included to illustrate how the Vasculome is integral to the function and malfunction of different organs, such as the brain or the kidney.

Each section is preceded by an introductory summary that will give a high level unified view of the key concepts illustrated in the various chapters in that section.

Zorina Galis' The Vasculome was named a finalist in the Clinical Medicine category of the American Association of Publishers’ 2023 PROSE Awards.

Cover image
Title page
Table of Contents
Companion website
Copyright
Contributors
Preamble
Acknowledgment
List of abbreviations
The architectural design of the vasculome: basis for system-wide functional unity and local diversity
Section 1. The endothelium: key unifying principle of the vasculome. Basis for systemic unity and for engineering of local specialization
Chapter 1. Development of, and environmental impact on, endothelial cell diversity
Introduction
Diversity of endothelial cell types
Endothelial cell diversity within adult organs
Impact of environmental factors on endothelial cell specification
Epigenetic and noncoding RNA regulation of endothelial cell phenotype
Summary and conclusions
Chapter 2. Endothelial cell heterogeneity and plasticity in health and disease—new insights from single-cell studies
Introduction
Endothelial cell heterogeneity and plasticity
Angiogenic EC phenotypes
EC metabolic heterogeneity
EC heterogeneity in tissue repair
EC heterogeneity in cancer
Perspectives and therapeutic implications
Section 2. Vasculome’s key building blocks—beyond the endothelium
Chapter 3. The remarkable diversity of vascular smooth muscle in development and disease: a paradigm for mesenchymal cell types
Introduction
The vascular system is a developmental mosaic
Assembly of the vessel wall in development
Self-organization guides artery wall development
Positional identity and VSMC diversity
VSMC differentiation, phenotypic switching, and reprogramming
VSMC reprogramming to multiple mesenchymal cell types
Role of Krüppel-like factor 4 in VSMC reprogramming
VSMC single-cell transcriptomes and VSMC reprogramming
VSMC single-cell transcriptomes and embryonic origins
Vascular smooth muscle clonal expansions in vivo
SMC diversity: one genome, many epigenomes
VSMCs—a paradigm for mesenchymal cell types
Does VSMC reprogramming extend “the vasculome” beyond the vascular system?
Chapter 4. Smooth muscle diversity in the vascular system
Introduction
Vascular smooth muscle cell diversity: contractile properties
Vascular smooth muscle cell diversity in vasomotor control and signaling networks
Alternative splicing to rewire signaling networks
Newer methodologies for the study of smooth muscle diversity
Conclusion
Chapter 5. Resident vascular immune cells in health and atherosclerotic disease
Macrophages
Granulocytes
Dendritic cells
CD4+ and CD8+ T cells
Other T cell subsets
B cells
Other lymphoid cells
Conclusion
Chapter 6. Perivascular adipose tissue: friend or foe?
Introduction
PVAT vascular functions
Perivascular adipose tissue implications in pathology
Conclusion
Chapter 7. Major vascular ECM components, differential distribution supporting structure, and functions of the vasculome
Structure and function of the vasculome
Major vascular ECM proteins
The ECM and its interactions with cells
Conclusions
Section 3. Putting it all together: vasculome integration across body scales and within tissues
Chapter 8. Out to the tissues: the arterial side (arteries, arterioles—development, structure, functions, and pathologies)
Introduction
The arterial wall: development, structure, and function
Arterial pathologies
Conclusion
Chapter 9. Capillary diversity: endothelial cell specializations to meet tissue metabolic needs
Introduction
Attributes of capillary endothelial cells
Maintenance and expansion of capillary networks
Endothelial control of nutrient delivery
Release of angiocrine factors to support tissue physiology
Endothelial cell role in immune surveillance
Indicators of tissue-specific endothelial cell plasticity?
Consequences of compromised endothelial cell performance
Conclusions
Chapter 10. The neurovascular unit and blood–CNS barriers in health and disease
The neurovascular unit and the blood–CNS barrier in the healthy state
CNS angiogenesis and BBB/BRB development
Vascular basement membrane and CNS vascular barrier maturation
The neurovascular unit and blood–CNS barriers in neurological and ocular diseases
Chapter 11. Lymphatic biology and medicine
Introduction
Lymphatic vasculature
Lymphangiogenesis
Lymphedema
Pathological conditions with lymphatic defects
Concluding remarks
Investigating the vasculome: context-driven methods, uses, and limitations
Section 1. Experimental and computational studies of the vasculome
Chapter 12. The flow-dependent endotheliome: hemodynamic forces, genetic programs, and functional phenotypes
Introduction
Flow patterns in the human circulation
Modeling human hemodynamic forces in vitro
Unraveling flow-dependent endothelial gene expression and functional phenotypes
Conclusions and future directions
Chapter 13. Intravital photoacoustic microscopy of microvascular function and oxygen metabolism
Introduction
Multiparametric PAM: the working principles
Intravital PAM of the skin microvasculature
Intravital PAM of the dorsal vasculature
Intravital PAM of the cerebral microvasculature
Intravital PAM of the microvasculature in other tissues and organs
Frontiers in intravital PAM of the microvasculature
Conclusion
Chapter 14. Systems biology modeling of endothelial cell and macrophage signaling in angiogenesis in human diseases
Introduction
Computational models of HIF stabilization and HIF-mediated cellular pathways in angiogenesis
Computational models of growth factor-mediated signaling pathways regulating angiogenesis
Computational multipathway models of endothelial cells and macrophages in angiogenesis
Discussion and future perspectives
Chapter 15. Simulation of blood flow and oxygen transport in vascular networks
Introduction
Simulation of blood flow
Simulation of oxygen transport
Discussion
Chapter 16. Clinical investigations of vascular function
Vascular endothelial function
Arterial stiffness
Conclusions
Appendix A. Supplementary data
Section 2. Realizing the promise of new high-content technologies
Chapter 17. Angiodiversity—A tale retold by comparative transcriptomics
Introduction
Chapter 18. Using pattern recognition and discriminant analysis of functional perfusion data to create “angioprints” for normal and perturbed angiogenic microvascular networks
Introduction
Overall experimental design
Results
Discussion
Methods
Experimental data
Automated pattern recognition and discrete optimization-based classification model for discriminant analysis
Image-based pattern recognition algorithm
Chapter 19. Artificial intelligence for the vasculome
Introduction
Conclusion
Vasculome dynamics: in health and in sickness
Section 1. Cooperating during development and organogenesis to create vasculome diversity
Chapter 20. Vascular development and organogenesis: depots of diversity among conduits of connectivity define the vasculome
Introduction
Historical perspective of the vasculome concept
Vascular development and organogenesis: where it all starts
Vascular development and organogenesis: location-dependent crosstalk
Circulation-dependent input for local vascular specialization
The vasculome: conclusions and future directions
Chapter 21. Normal vascular identity (arteries, veins, and lymphatics) and malformations
Introduction
Vasculogenesis: arteriovenous differentiation
Angiogenesis: sprouting angiogenesis
Establishing vascular identity
Vascular malformations
Vascular tumors
Switching of arterial–venous identity
Summary
Chapter 22. Sprouting angiogenesis in vascular and lymphatic development
Vascular development
Sprouting angiogenesis
Vascular endothelial growth factor and regulation of tip cell formation
Guidance receptor signaling
The Notch directive: tip or stalk?
Refinement of sprouting angiogenesis by BMP signals
Lymphatic development
Section 2. Physiological and pathological remodeling of the vasculome
Chapter 23. Enablers and drivers of vascular remodeling
Introduction
Brief on vascular mechanics
Biological and physiological consequences of mechanics
Mechanobiology and SMC phenotype
ECM turnover in evolving mechanical states
Mechanical homeostasis—an organizing principle
Conclusion
Appendix 1
Chapter 24. Extracellular matrix dynamics and contribution to vascular pathologies
Atherosclerosis
Vascular calcification
Arterial stiffening
Aneurysms
Limitations and areas needing further study
Chapter 25. Lymphatic vascular anomalies and dysfunction
Introduction
Lymphatic vascular tumors
Lymphatic malformations
Lymphatic malformations associated with other vascular malformations or overgrowth syndromes
Primary lymphedema
Conclusions
Part IV. The vasculome as perpetrator and victim in local and systemic diseases
Chapter 26. Endothelial dysfunction: basis for many local and systemic conditions
Introduction
Physiological role of endothelial (vascular) function
Mechanisms of endothelial dysfunction
Therapeutic prevention of endothelial (vascular) dysfunction
Conclusions and clinical implications
Chapter 27. The vascular phenotype in hypertension
Introduction
Vascular function: integration of vascular smooth muscle contraction/relaxation
Vascular remodeling in hypertension
The immune system and inflammation—a new paradigm in the vascular phenotype in hypertension
Perivascular adipose tissue influences vascular function in hypertension
Vascular aging in hypertension
Conclusions
Chapter 28. Functional roles of lymphatics in health and disease
Introduction
Lymphatics in adipose metabolism and obesity
Lymphatics in skin regeneration
Lymphatics in the central nervous system
Alzheimer's disease
Aging
Lymphatic function in aqueous drainage and glaucoma
Lymphatics in cardiovascular disease
Atherosclerosis
Myocardial infarction
Conclusions
Chapter 29. Extracellular matrix genetics of thoracic and abdominal aortic diseases
Thoracic aortic aneurysms predispose to acute aortic dissections
Heritable thoracic aortic disease genetics highlights the importance of maintaining an aortic structural component, the elastin-contractile unit
The genetics of abdominal aortic aneurysms
The extracellular matrix in genetics of aortic disease
Chapter 30. Peripheral arterial disease (pathophysiology, presentation, prevention/management)
Introduction
PAD: epidemiology and risk factors
Diagnosis and initial evaluation
Spectrum of disease
Pathophysiology and pathobiology
Disease management
PAD therapies in development
Conclusions
Chapter 31. Venous diseases including thromboembolic phenomena
Venous thrombogenesis with special emphasis on selectins
Venous thrombosis and resolution
Pre-clinical/basic science models
Preclinical/translational models
Research reproducibility/comparative pathology/statistical consultation
New areas of venous research in thrombogenesis, resolution, and novel approaches for the future
Part V. The vasculome in diagnosis, prevention, and treatment of other diseases
Chapter 32. Targeting vascular zip codes: from combinatorial selection to drug prototypes
Introduction
A brief history of phage display
In vivo phage display and vascular zip codes
Human vascular mapping project
Translational/clinical applications
Bone Metastasis Targeting Peptidomimetic-11 (BMTP-11)
Adipotide
Other zip codes
Conclusions
Chapter 33. Angiosome concept for vascular interventions
Introduction
Clinical implementation of the angiosome model in the current treatment of CLTI
Summary
Chapter 34. RNA therapies for cardiovascular disease
Introduction to RNA therapeutics
RNA therapeutics in lipid disorders
Emerging RNA therapeutics for cardiac transthyretin amyloidosis
Future perspectives
Chapter 35. The brain vasculome: an integrative model for CNS function and disease
Introduction
Vasculome modifying factors
Cell–Cell interactions
Levels of vasculome mapping
The functional vasculome
Conclusions and future directions
Part VI. Looking forward toward “Precision Health” for the vasculome
Chapter 36. Vasculome: defining and optimizing vascular health
Introduction
Conclusion
Chapter 37. The Vasculome provides a body-wide cellular positioning system and functional barometer. The “Vasculature as Common Coordinate Frame (VCCF)” concept
Key requirements for a common coordinate frame (CCF) for the human body
Evaluating the vasculature as CCF and road map for the human body
Practical considerations for using the vasculature as a human body CCF
Vasculature as a barometer of functional tissue status and health
Parting thoughts
Index

Zorina S. Galis

Dr. Zorina Galis has been a life-long vascular researcher, recognized thought leader, innovator, highly cited researcher, mentor, and a popular science educator. She was educated in physics, biophysics, cell biology, pathology, and vascular medicine at the University of Bucharest, Romania, the McGill School of Medicine, Montreal, Canada, and the Harvard School of Medicine, Boston, USA. A prominent feature of Dr. Galis’ career has been to capitalize on her own transdisciplinary training and experience to identify and pursue major scientific and implementation challenges requiring a diversity of expertise. She has created, mentored, and led such teams, first, in academic medicine, as a tenured professor of Medicine/Cardiology and Biomedical Engineering at Emory School of Medicine and the Georgia Institute of Technology, then, as a Cardiovascular pharmaceutical industry executive at Eli Lilly and Company, and, currently, at the National Institutes of Health (NIH). Her best known research works are related to pioneering hypotheses about the molecular bases of acute cardiovascular conditions, which have led to the development of new diagnostic and therapeutic interventions (Google Scholar) https://scholar.google.com/citations?user=Qwwqn60AAAAJ&hl=en Since joining the in 2011 as the Chief of the Vascular Biology and Hypertension Branch in the National Heart Lung and Blood Institute (NHLBI), Dr. Galis has continued to create and lead wide partnerships dedicated to enhancing fundamental vascular knowledge and its translation, including the Trans-NIH Small Blood Vessels in Health and Disease and the Trans-NIH Lymphatic Coordination Committee, and has spearheaded funding opportunities, including the NHLBI Vascular Interventions/Innovations and Therapeutic Advances (VITA) Program and the NIH Common Fund Human BioMolecular Atlas Program (HuBMAP), both recognized with NHLBI and NIH Director Collaboration Awards. She serves on external professional advisory boards, and is a proud North American Vascular Biology Organization founding member and past Councilor. Of note: Contributions by Zorina Galis, Ph.D, to “The Vasculome” book have been provided in a personal capacity and do not necessarily reflect the opinions or endorsement of the National Institutes of Health (NIH), Department of Human Health Services (HHS).

Affiliations and expertise

Vascular Researcher, Editor, The Vasculome. Bethesda, MD, United States

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