Slevin Therapeutic Angiogenesis for Vascular Diseases

Molecular Mechanisms and Targeted Clinical Approaches for the Treatment of Angiogenic Disease
1. Auflage 2010
ISBN: 978-90-481-9495-7
Verlag: Springer Netherlands
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 430 Seiten

Reihe: Biomedical and Life Sciences (R0)

Angiogenesis is the growth of new blood vessels and is a key process which occurs during pathological disease progression. Excessive and damaging angiogenesis occurs in diseases such as cancer, diabetic retinopathies, age-related macular degeneration and atherosclerosis. In other diseases such as stroke and myocardial infarction, insufficient or improper angiogenesis results in tissue loss and ultimately higher morbidity and mortality. In this book we will begin by providing the reader with an overview of the process of angiogenesis including normal embryological development of blood vessels. The following chapters will each focus on a key angiogenic disease incorporating current scientific knowledge concerning the causes of activation of the “angiogenic switch”, pathological consequences, current treatment options and future perspectives. Where appropriate, results from pre-clinical trials, novel imaging modalities and nanotechnological approaches will be incorporated into these sections. Finally, since it is now believed that the process of angiogenesis operated via different signalling mechanisms in different vascular beds, we will discuss our current understanding of this phenomenon. The target audience for this book would include researchers in all the basic sciences; post-graduate students at Universities and Institutes; pharmaceutical industries; clinicians working in vascular biology or tissue imaging; pathologists; neurologists; tumour biologists; ophthalmologists and cardiologists.

Autoren/Hrsg.

Slevin, Mark

Inhaltsverzeichnis

1;Foreword;5
2;Preface;7
3;Contents;10
4;Contributors;12
5;1 Modified 3D-Fibrin Matrices in Tissue Engineeringfor Stimulation of Angiogenesis and Wound Healing;16
5.1;1.1 Introduction;17
5.2;1.2 Endothelial Cells and Their Functions in the Vascular System;18
5.2.1;1.2.1 Importance of Appropriate Extra-Cellular Matrix-Contacts for Endothelial Cells;20
5.2.2;1.2.2 The Importance of avß3 Integrin for Endothelial CellSurvival, Induction and Maintenance of Angiogenesis;21
5.2.3;1.2.3 Further Functions of avß3-integrin in AngiogenicEndothelial Cells: Co-operation with Growth FactorReceptors and Association with Matrix Metalloproteases;23
5.3;1.3 Hydrogels May be used as Substitutes for Native Extra-Cellular Matrix in Tissue Engineering;25
5.3.1;1.3.1 Fibrin Hydrogel Matrices for Increasing Angiogenesis and Improvement of Wound Healing;26
5.3.2;1.3.2 Modified 3D-Fibrin Matrices to Induce Angiogenesis;27
5.3.3;1.3.3 Fibrin Matrices as Combined Scaffold- and Drug Release Systems;27
5.3.4;1.3.4 3D-Fibrin Matrices Containing Homogeneously-Distributed and Gradients of Cell Guidance Cues;29
5.4;1.4 Conclusions and Outlook;29
5.5;References;32
6;2 Ocular Retinopathies and Clinical Control of Angiogenesis;42
6.1;2.1 Introduction of Ocular Neovascular Disorders;43
6.1.1;2.1.1 General Features of Ocular Neovascular Disorders;43
6.1.2;2.1.2 Corneal Neovascularization;47
6.1.3;2.1.3 Age-Related Macular Degeneration;49
6.1.4;2.1.4 Diabetic Retinopathy;50
6.1.5;2.1.5 Other Retinal Neovascular Diseases;52
6.2;2.2 Proangiogenic Factors in Ocular Neovascularization;53
6.2.1;2.2.1 General Features of Pro-Angiogenic Factors;53
6.2.2;2.2.2 Vascular Endothelial Cell Growth Factor;53
6.2.3;2.2.3 Insulin Growth Factor-1;56
6.2.4;2.2.4 Erythropoietin;57
6.3;2.3 Anti-Angiogenic Factors in the Eye;58
6.3.1;2.3.1 General Features of Anti-Angiogenic Factors;58
6.3.2;2.3.2 Pigment Epithelium-Derived Factor;59
6.3.3;2.3.3 Thrombospondin;61
6.3.4;2.3.4 Angiostatin;62
6.3.5;2.3.5 Kallikrein-binding Protein;62
6.4;2.4 Pathogenic Roles of the Wnt Pathway in Age-Related Macular Degeneration, Retinopathy of Prematurity and Diabetic Retinopathy;63
6.4.1;2.4.1 The Wnt Pathway;63
6.4.2;2.4.2 Mutations of Wnt Related Proteins in Neovascular Diseases in the Eye;65
6.4.3;2.4.3 Wnt Signaling Plays a Pathogenic Role in Ocular NV;65
6.4.4;2.4.4 The Wnt Pathway and Pro- and Anti-Angiogenic Factors;66
6.4.5;2.4.5 The Wnt Pathway, a New Drug Target for the Treatment of Ocular NV;67
6.5;References;67
7;3 Angiogenic Gene Therapy for the Treatment of Retinopathies;81
7.1;3.1 Introduction;82
7.2;3.2 Gene Therapy: Basic Principles;83
7.2.1;3.2.1 Gene Delivery Techniques and Vector Design;83
7.2.2;3.2.2 Target Selection and Strategic Considerations;84
7.2.3;3.2.3 siRNA and Cell-Based Approaches;87
7.3;3.3 Ocular Gene Therapy for Non-Neovascular Retinal Disease: Early Successes and Difficulties in a Fledgling Enterprise;87
7.4;3.4 Investigative Strategies for Angiogenic Gene Therapy of Neovascular Retinopathies;89
7.5;3.5 Ad Pigment Epithelial-Derived Factor for Choroidal Neovascularization in Macular Degeneration: The First Angiogenic Gene Therapy Trial for a Neovascular Retinopathy;90
7.6;3.6 Summary and Future Directions;90
7.7;References;91
8;4 Angiogenesis in Tumour Development and Metastasis;95
8.1;4.1 Initiation of Tumour Angiogenesis;96
8.1.1;4.1.1 Initiation of Angiogenesis;96
8.1.2;4.1.2 VEGF and VEGF Receptors;97
8.1.3;4.1.3 Cellular Action of VEGF;97
8.1.4;4.1.4 Endothelial Tip and Stalk Cells;98
8.1.5;4.1.5 Notch Pathway;98
8.1.6;4.1.6 Dll4 and Notch in Tumour Angiogenesis;100
8.2;4.2 Progression of Tumour Angiogenesis;101
8.2.1;4.2.1 Physiological Vessel Maturation;101
8.2.2;4.2.2 Tumour Vessel Maturation;101
8.3;4.3 Metastasis;102
8.3.1;4.3.1 Angiogenesis and the Pre-metastatic Niche;102
8.3.2;4.3.2 Angiogenesis and Cancer Cell Transit: Intravasation and Extravasation;102
8.3.3;4.3.3 Angiogenesis and the Transition from Micro- to Macrometastases;103
8.4;4.4 Tumour Lymphangiogenesis;103
8.4.1;4.4.1 VEGF-C and VEGFR-3;104
8.4.2;4.4.2 VEGFR-3 in Tumour Biology;104
8.5;References;104
9;5 Cancer Therapy by Targeting Vascular Endothelial Cell Growth Factor- and Non-Vascular Endothelial Cell Growth Factor-Mediated Angiogenesis;108
9.1;5.1 Multiple Factors Contribute to the Angiogenic Switch in Tumors;109
9.2;5.2 Spatiotemporal Interaction Between Vascular Endothelial Cell Growth Factor and Other Factors;110
9.3;5.3 Reciprocal Interplay Between Fibroblast Growth Factor-2 and Platelet-Derived Growth Factor-B;114
9.4;5.4 Hypoxia Induces a Shift of Functional Interplay Between Growth Factors;116
9.5;5.5 Therapeutic Implications and Drug Resistance;117
9.6;5.6 Perspectives;121
9.7;References;122
10;6 Molecular Mechanisms of Post-Ischemic Angiogenesis in the Brain;127
10.1;6.1 Angiogenesis After Cerebral Ischemia;128
10.2;6.2 Temporal Course of Post-Ischemic Angiogenesis in the Brain;128
10.3;6.3 Gene Expression Studies Following Stroke;130
10.3.1;6.3.1 Hypoxia Inducible Factor-1;130
10.3.2;6.3.2 Hypoxia Inducible Factor-2 Alpha;131
10.3.3;6.3.3 Vascular Endothelial Growth Factor;131
10.3.4;6.3.4 Vascular Endothelial Growth Factor Receptors;133
10.3.4.1;6.3.4.1 Neuropilins;134
10.3.4.2;6.3.4.2 Tie Receptor System;134
10.3.4.3;6.3.4.3 Angiopoietins;135
10.4;6.4 Endothelial Progenitor Cells and Their Involvement in Post-Ischemic Angiogenesis;137
10.5;6.5 Therapeutic Angiogenesis and Vasculogenesis;138
10.6;6.6 Pharmacological Approach to Enhance Angiogenesis;139
10.7;6.7 Physical Activity to Increase Post-Ischemic Angiogenesis;144
10.8;6.8 Cellular Approach to Increase Post-Ischemic Angiogenesis;144
10.9;6.9 Remarks;146
10.10;References;146
11;7 Angiogenesis, the Neurovascular Niche and Neuronal Reintegration After Injury;156
11.1;7.1 Introduction;157
11.2;7.2 Structure/Composition/Functions of the Neurovascular Niches;158
11.3;7.3 In Vitro Models of the Neurovascular Niche;160
11.4;7.4 Coupled Angiogenesis and Neurogenesis in the Neurovascular Niche Following Central Nervous System (CNS) Injury: In Vivo and In Vitro Models of the Neurovascular Niche Potential Usefulness for Mechanistic Studies, Therapeutic Screens and Therapy;166
11.5;7.5 Conclusions Future Directions;171
11.6;References;172
12;8 Safe and Effective Vascular Endothelial Cell Growth Factor (VEGF)-based Therapeutic Angiogenesis for Ischemic Stroke: Insights from Preclinical Trials;179
12.1;8.1 Challenges of Treatments for Ischemic Stroke;181
12.1.1;8.1.1 Epidemiology of Stroke;181
12.1.2;8.1.2 Limitations of Current Treatments for Ischemic Stroke;182
12.2;8.2 Vascular Endothelial Cell Growth Factor, Neuroprotection and Vascular Endothelial Cell Growth Factor-Based Therapeutic Angiogenesis for Ischemic Stroke;183
12.2.1;8.2.1 Neuroprotection as a New Treatment for Ischemic Stroke;183
12.2.2;8.2.2 Therapeutic Angiogenesis as a Treatment for Ischemic Stroke;184
12.2.3;8.2.3 Basics of Vascular Endothelial Cell Growth Factor;185
12.2.4;8.2.4 Potential Clinical Benefits of Vascular Endothelial Cell Growth Factor-based Therapeutic Angiogenesis;186
12.2.5;8.2.5 Potential Adverse Effects of Vascular Endothelial Cell Growth Factor-based Therapeutic Angiogenesis;187
12.3;8.3 Gaps in Knowledge Regarding Safety and Efficacy of Vascular Endothelial Cell Growth Factor-based Therapeutic Angiogenesis for Ischemic Stroke;188
12.3.1;8.3.1 Does Vascular Endothelial Cell Growth Factor-based Therapeutic Angiogenesis Promote or Hinder Neuroprotection of Ischemic Nervous Tissue, and Does the Induced Angiogenesis Damage the Microanatomy of Normal (Non-ischemic) Tissue?;188
12.3.2;8.3.2 Do Doses of Vascular Endothelial Cell Growth Factor That Appear to be Neuroprotective at the Light Microscopy Level Cause Clinically-significant Ultrastructural Alterations of the Neurovascular Unit?;189
12.3.3;8.3.3 Does Vascular Endothelial Cell Growth Factor Combination Therapy Provide Greater Neuroprotection over Vascular Endothelial Cell Growth Factor Monotherapy Without Increasing the Adverse Effects?;195
12.3.4;8.3.4 What is the Best Route, Timing and Duration for Administering Vascular Endothelial Cell Growth Factor, and How Do These Parameters Influence Inflammation?;197
12.3.5;8.3.5 What are the Relationships between Exogenous Vascular Endothelial Cell Growth Factor, Existing Tissue Injury, and Inflammation?;199
12.3.6;8.3.6 What is the Best Vascular Endothelial Cell Growth Factor Isoform for Therapeutic Angiogenesis, and How Does It Affect the Anatomy and Physiology of Other Organs?;199
12.3.7;8.3.7 Does Vascular Endothelial Cell Growth Factor-Based Therapeutic Angiogenesis Compromise Systemic Hemodynamics?;200
12.3.8;8.3.8 How Would the Beneficial and Adverse Outcomes of Vascular Endothelial Cell Growth Factor-based Therapeutic Angiogenesis Differ in Various Stroke Models, Particularly with Differences in Age, Gender or Coexisting Chronic Diseases?;202
12.3.8.1;8.3.8.1 Permanent and Transient Stroke Models;202
12.3.8.2;8.3.8.2 Different Animal Species;202
12.3.8.3;8.3.8.3 Short-Term and Long-Term Evaluations with Constant Physiology Monitoring;203
12.3.8.4;8.3.8.4 Gender-Based Stroke Models;204
12.3.8.5;8.3.8.5 Age-Based Stroke Models;204
12.3.8.6;8.3.8.6 Chronic Disease-Based Stroke Models;205
12.3.9;8.3.9 Are Gene Therapy and Stem Cells Beneficial for Vascular Endothelial Cell Growth Factor-based Therapeutic Angiogenesis for Stroke?;205
12.4;8.4 Conclusions;207
12.5;References;208
13;9 Atherosclerotic Plaque Angiogenesis as a Mechanism of Intraplaque Hemorrhage and Acute Coronary Rupture;223
13.1;9.1 The Vasa Vasorum as a Physiologic Structure of the Normal Vessel Wall;225
13.2;9.2 The Natural Progression of Human Atherosclerosis by Lesion Morphology;226
13.3;9.3 The Paradigm of Erythrocyte-Derived Cholesterol and Lesion Destabilization;228
13.4;9.4 Plaque NeovascularizationA Substantive Component of Atherosclerosis;229
13.5;9.5 Evidence for an Angiogenic Switch Hypothesis in Atherosclerotic Plaques;229
13.6;9.6 Hypoxia-Driven Neovascularization in Atherosclerosis;232
13.7;9.7 Extra-Pericellular Proteolysis, the Choreographers of Pathologic Angiogenesis;235
13.8;9.8 Rapid Endothelial Response Proteins Control of Angiogenesis and Permeability;236
13.9;9.9 Selective Factors Controlling Endothelial Permeability;237
13.9.1;9.9.1 Angiopoietin-Tie2 Signaling;237
13.9.2;9.9.2 The Bioactive Lipid, Sphingosine-1-Phosphate;237
13.10;9.10 The Role of Tissue Macrophages as Modifiers of Angiogenic Responses;238
13.11;9.11 The Concept of Normalization of Blood Vessels to Prevent Hemorrhagic Events in Plaques;239
13.12;9.12 Concluding Remarks and Future Perspectives;241
13.13;References;241
14;10 Neovascularization and Intra-plaque Hemorrhage: Role of Haptoglobin, Macrophages, and Heme-Oxygenase-1 Pathway;247
14.1;10.1 Introduction;248
14.2;10.2 Neovascularization as a Defense Mechanism;248
14.2.1;10.2.1 Response to Injury: Granulation Tissue;249
14.2.2;10.2.2 Neovascularization and Adventitial Remodeling;249
14.2.3;10.2.3 Neovascularization and Plaque Regression;251
14.3;10.3 Failure of Neovessels: Intraplaque Hemorrhage;252
14.3.1;10.3.1 Extravasation of Red Blood Cells and Lipid Deposition;254
14.3.2;10.3.2 Extracorpuscular Hemoglobin and Oxidative Stress;254
14.4;10.4 Haptoglobin;255
14.4.1;10.4.1 Haptoglobin Genotype and Protein Structure in Humans;255
14.4.2;10.4.2 Role of Haptoglobin Genotype in Human Atherosclerosis;256
14.4.2.1;10.4.2.1 Macrophage Activation and Infiltration;257
14.4.2.2;10.4.2.2 Iron Deposition in Plaque Tissue;258
14.4.2.3;10.4.2.3 Reverse Cholesterol Transport;258
14.5;10.5 The Macrophage Scavenger Receptor CD163;259
14.5.1;10.5.1 Downregulation of CD163 Gene and Protein Expression in Diabetes Mellitus;259
14.6;10.6 Heme Oxygenase-1;260
14.6.1;10.6.1 Increased HO-1 Protein in Plaques with Intraplaque Hemorrhage;261
14.6.2;10.6.2 Role of Heme Oxygenase-1 in Diabetes-Related Atherosclerosis;262
14.7;10.7 Summary;262
14.8;References;263
15;11 Angiogenic Approaches for Inhibition of Plaque Destabilization in Atherosclerosis;267
15.1;11.1 Introduction;268
15.2;11.2 Role of Neovascularization in Destabilization of the Vulnerable Plaque;268
15.3;11.3 Imaging Techniques of Vasa Vasorum;270
15.4;11.4 Therapeutic Approaches for Inhibition of Plaque Neovascularization;271
15.4.1;11.4.1 Systemic Anti-Neoangiogenetic Agents;272
15.4.2;11.4.2 Local Antiangiogenic Therapy;272
15.5;11.5 Future Directions;273
15.6;References;274
16;12 A Key Role of Angiogenic Control in Recovery from Ischaemic Heart Disease;276
16.1;12.1 Introduction;277
16.2;12.2 Challenges for Ischaemic Heart Disease: Myogenesis and Angiogenesis;278
16.3;12.3 Myocardial Plasticity/Regeneration;278
16.3.1;12.3.1 Evidence for Cardiomyocyte Repopulation in Postnatal Hearts;279
16.3.2;12.3.2 Sources of Cardiogenic Cells;281
16.3.2.1;12.3.2.1 Bone Marrow Derived Stem Cells;281
16.3.2.2;12.3.2.2 Resident Cardiac Stem Cells;282
16.3.2.3;12.3.2.3 Stem Cells in the Periphery and/or Circulation;284
16.3.2.4;12.3.2.4 Cell-Based Cardiac Repair with Exogenous Pluripotent Stem Cells;284
16.4;12.4 Myocardial Repair: The Burden of Remodelling;285
16.5;12.5 Angiogenesis;287
16.5.1;12.5.1 Principle;287
16.5.2;12.5.2 Mechanism of Angiogenesis;288
16.5.3;12.5.3 Sprouting and Non-sprouting Angiogenesis;289
16.5.4;12.5.4 Angiogenesis Post Myocardial Ischaemia;291
16.5.5;12.5.5 Role of Inflammation;291
16.5.6;12.5.6 Growth Factors, Cytokines and Angiogenesis;292
16.6;12.6 Therapeutic Potential of Angiogenesis;294
16.6.1;12.6.1 Cell Therapy for Therapeutic Angiogenesis: Experimental Evidence;294
16.6.2;12.6.2 Cell Therapy for Therapeutic Angiogenesis: Human Trials;295
16.6.3;12.6.3 Growth Factors and Cytokines for Therapeutic Angiogenesis;297
16.6.4;12.6.4 Vascular Endothelial Cell Growth Factor for Therapeutic Angiogenesis;297
16.6.5;12.6.5 Other Options for Therapeutic Angiogenesis;298
16.7;12.7 Conclusion;299
16.8;References;300
17;13 Angiogenic Mediators and the Pathogenesis of Alzheimer'sDisease;304
17.1;13.1 Introduction;305
17.2;13.2 Vascular Changes in Alzheimers Disease;306
17.2.1;13.2.1 Loss of Vascular Density;306
17.2.2;13.2.2 Amyloid Angiopathy;307
17.3;13.3 Angiogenic Mediators in the Brain Vasculature in Alzheimers Disease;308
17.3.1;13.3.1 Pro-Angiogenic Factors;310
17.3.2;13.3.2 Angiogenic Inhibitors;311
17.3.3;13.3.3 Angiogenic Signaling Mechanisms;312
17.4;13.4 Effects of Anti-Angiogenic Drugs in the Brain;313
17.5;13.5 Activated-Angiogenic Vasculature in AD: A New Paradigm of Disease Pathogenesis;314
17.6;13.6 Conclusions and Future Directions;316
17.7;References;316
18;14 Vascular Development, Stroke and Neurodegenerative Disease: A Place for Novel Clinical Interventions?;322
18.1;14.1 Introduction;323
18.2;14.2 Neurorepair: Plasticity, Neurogenesis and Angiogenesis;324
18.3;14.3 Significance of the Neurovascular Unit;325
18.4;14.4 Angiogenesis;326
18.4.1;14.4.1 Occurrence and Importance;326
18.4.2;14.4.2 Mechanisms of Angiogenesis After Stroke;326
18.4.2.1;14.4.2.1 Animal Models of Stroke;326
18.4.2.2;14.4.2.2 Human Studies;327
18.5;14.5 Stroke and Neurodegenerative Disease;328
18.5.1;14.5.1 Common Risk Factors;328
18.5.1.1;14.5.1.1 Genetic Risk Factors;329
18.5.2;14.5.2 Stroke and Vascular Dementia;331
18.5.3;14.5.3 Lacunar Stroke and Alzheimer's Disease;333
18.5.4;14.5.4 Lacunar Stroke and Vascular Cognitive Impairment;335
18.6;14.6 Therapeutic Potential of Angiogenesis;339
18.7;14.7 Conclusions and Perspectives;340
18.8;References;340
19;15 Peripheral Artery Disease and Angiogenesis: A Link Between Angiogenesis and Atherothrombosis;348
19.1;15.1 Introduction;349
19.2;15.2 Thrombogenesis and Atherogenesis in Peripheral Artery Disease;350
19.2.1;15.2.1 Thrombogenesis;350
19.2.2;15.2.2 Atherogenesis;352
19.3;15.3 Angiogenesis;355
19.3.1;15.3.1 Angiogenesis and Coagulation;357
19.3.2;15.3.2 Angiogenesis and Atherogenesis;357
19.3.3;15.3.3 The Endothelium: A Link Between Angiogenesis, Atherogenesis and Thrombogenesis;360
19.4;15.4 Therapeutic Angiogenesis in Peripheral Vascular Disease;361
19.5;15.5 Conclusions;363
19.6;References;364
20;16 Role of Angiogenesis in the Pathogenesis of Arthritis: Potential Therapeutic Applications;369
20.1;16.1 Introduction;370
20.1.1;16.1.1 Causes, Symptoms, and Complications of Rheumatoid Arthritis;370
20.1.2;16.1.2 Treatment of Rheumatoid Arthritis;372
20.2;16.2 Angiogenesis: A Key Role in Rheumatoid Arthritis;373
20.2.1;16.2.1 Growth Factors Regulating Angiogenesis in Rheumatoid Arthritis;374
20.2.2;16.2.2 Hypoxia as a Trigger for Angiogenesis in Rheumatoid Arthritis;375
20.3;16.3 New Therapeutic Approaches in Rheumatoid Arthritis;377
20.3.1;16.3.1 Potential for Angiogenesis Inhibition in Rheumatoid Arthritis;377
20.3.2;16.3.2 Targeting Hypoxia in Rheumatoid Arthritis;379
20.4;16.4 Conclusions;383
20.5;References;383
21;17 Angiogenesis and Giant Cell Arteritis;391
21.1;17.1 Introduction: Giant Cell Arteritis;392
21.2;17.2 Angiogenesis in Giant Cell Arteritis;396
21.2.1;17.2.1 Angiogenesis in the Inflamed Artery of Giant Cell Arteritis;396
21.2.1.1;17.2.1.1 Inflammation and Hypoxia in GCA;396
21.2.1.2;17.2.1.2 Demonstration of Angiogenesis by Immunohistochemistry in GCA;397
21.2.1.3;17.2.1.3 Angiogenesis and Inflammatory Cell Recruitment;398
21.2.1.4;17.2.1.4 Angiogenesis and Intimal Hyperplasia;399
21.2.1.5;17.2.1.5 Functional Relevance of Endothelial Markers in Giant Cell Arteritis;399
21.2.2;17.2.2 Angiogenic Mediators in the Temporal Artery;400
21.2.2.1;17.2.2.1 Vascular Endothelial Cell Growth Factor;400
21.2.2.2;17.2.2.2 Platelet Derived Growth Factor;400
21.2.2.3;17.2.2.3 Monocyle Chemotactic Protein-1;401
21.2.2.4;17.2.2.4 Transforming Growth Factor-;401
21.2.2.5;17.2.2.5 iNOS;401
21.2.2.6;17.2.2.6 Other Possible Angiogenic Mediators in the Temporal Artery;401
21.2.3;17.2.3 Angiogenesis, Intimal Hyperplasia and Systemic Inflammation;402
21.2.3.1;17.2.3.1 Systemic Inflammatory Mediators and Angiogenesis in Ischaemic Organs;403
21.2.3.2;17.2.3.2 Hyperpermeability of Microvessels;404
21.3;17.3 Treatment of Giant Cell Arteritis and Angiogenesis;404
21.3.1;17.3.1 Steroids;404
21.3.2;17.3.2 Steroid-Sparing Agents;405
21.3.3;17.3.3 Selection of Therapies for Co-morbid Cardiovascular Diseases;405
21.4;17.4 Conclusions and Future Directions;406
21.5;References;406
22;18 Moyamoya Disease;411
22.1;18.1 Background;412
22.2;18.2 Epidemiology;412
22.3;18.3 Pathology and Pathophysiology;414
22.4;18.4 Clinical Features;415
22.5;18.5 Moyamoya Syndromes;417
22.6;18.6 Diagnosis;417
22.7;18.7 Treatment Options for Moyamoya Disease;420
22.8;References;422
23;19 Overview on Nanotechnology and Angiogenesis in Major Diseases Processes;425
23.1;19.1 State-of-Art: Angiogenesis and Nanotechnology;426
23.2;19.2 Nanotechnology;426
23.2.1;19.2.1 Overview on Nanomedicine;426
23.2.2;19.2.2 Nanosystems Applied to Medicine;426
23.2.3;19.2.3 Nano-Diagnosis and Medical Imaging;427
23.2.4;19.2.4 Nano-Based Drug Delivery Systems;427
23.2.5;19.2.5 Nano-Based Drug Delivery Systems Market;428
23.3;19.3 Nanomedicine Applications in Angiogenesis;428
23.3.1;19.3.1 Oncology;429
23.3.2;19.3.2 Cardiology;429
23.3.3;19.3.3 Ophthalmology;430
23.3.4;19.3.4 Imaging of Angiogenesis;430
23.4;19.4 Conclusions;431
23.5;References;431
24;Index;433