Book contents
- Frontmatter
- Contents
- Editor, Associate Editors, Artistic Consultant, and Contributors
- Preface
- PART I CONTEXT
- PART II ENDOTHELIAL CELL AS INPUT-OUTPUT DEVICE
- 27 Introductory Essay: Endothelial Cell Input
- 28 Hemodynamics in the Determination of Endothelial Phenotype and Flow Mechanotransduction
- 29 Hypoxia-Inducible Factor 1
- 30 Integrative Physiology of Endothelial Cells: Impact of Regional Metabolism on the Composition of Blood-Bathing Endothelial Cells
- 31 Tumor Necrosis Factor
- 32 Vascular Permeability Factor/Vascular Endothelial Growth Factor and Its Receptors: Evolving Paradigms in Vascular Biology and Cell Signaling
- 33 Function of Hepatocyte Growth Factor and Its Receptor c-Met in Endothelial Cells
- 34 Fibroblast Growth Factors
- 35 Transforming Growth Factor-β and the Endothelium
- 36 Thrombospondins
- 37 Neuropilins: Receptors Central to Angiogenesis and Neuronal Guidance
- 38 Vascular Functions of Eph Receptors and Ephrin Ligands
- 39 Endothelial Input from the Tie1 and Tie2 Signaling Pathway
- 40 Slits and Netrins in Vascular Patterning: Taking Cues from the Nervous System
- 41 Notch Genes: Orchestrating Endothelial Differentiation
- 42 Reactive Oxygen Species
- 43 Extracellular Nucleotides and Nucleosides as Autocrine and Paracrine Regulators within the Vasculature
- 44 Syndecans
- 45 Sphingolipids and the Endothelium
- 46 Endothelium: A Critical Detector of Lipopolysaccharide
- 47 Receptor for Advanced Glycation End-products and the Endothelium: A Path to the Complications of Diabetes and Inflammation
- 48 Complement
- 49 Kallikrein-Kinin System
- 50 Opioid Receptors in Endothelium
- 51 Snake Toxins and Endothelium
- 52 Inflammatory Cues Controlling Lymphocyte–Endothelial Interactions in Fever-Range Thermal Stress
- 53 Hyperbaric Oxygen and Endothelial Responses in Wound Healing and Ischemia–Reperfusion Injury
- 54 Barotrauma
- 55 Endothelium and Diving
- 56 Exercise and the Endothelium
- 57 The Endothelium at High Altitude
- 58 Endothelium in Space
- 59 Toxicology and the Endothelium
- 60 Pericyte–Endothelial Interactions
- 61 Vascular Smooth Muscle Cells: The Muscle behind Vascular Biology
- 62 Cross-Talk between the Red Blood Cell and the Endothelium: Nitric Oxide as a Paracrine and Endocrine Regulator of Vascular Tone
- 63 Leukocyte–Endothelial Cell Interactions
- 64 Platelet–Endothelial Interactions
- 65 Cardiomyocyte–Endothelial Cell Interactions
- 66 Interactions between Hepatocytes and Liver Sinusoidal Endothelial Cells
- 67 Stellate Cell–Endothelial Cell Interactions
- 68 Podocyte–Endothelial Interactions
- 69 Introductory Essay: Endothelial Cell Coupling
- 70 Endothelial and Epithelial Cells: General Principles of Selective Vectorial Transport
- 71 Electron Microscopic–Facilitated Understanding of Endothelial Cell Biology: Contributions Established during the 1950s and 1960s
- 72 Weibel-Palade Bodies: Vesicular Trafficking on the Vascular Highways
- 73 Multiple Functions and Clinical Uses of Caveolae in Endothelium
- 74 Endothelial Structures Involved in Vascular Permeability
- 75 Endothelial Luminal Glycocalyx: Protective Barrier between Endothelial Cells and Flowing Blood
- 76 The Endothelial Cytoskeleton
- 77 Endothelial Cell Integrins
- 78 Aquaporin Water Channels and the Endothelium
- 79 Ion Channels in Vascular Endothelium
- 80 Regulation of Angiogenesis and Vascular Remodeling by Endothelial Akt Signaling
- 81 Mitogen-Activated Protein Kinases
- 82 Protein Kinase C
- 83 Rho GTP-Binding Proteins
- 84 Protein Tyrosine Phosphatases
- 85 Role of β-Catenin in Endothelial Cell Function
- 86 Nuclear Factor-κB Signaling in Endothelium
- 87 Peroxisome Proliferator-Activated Receptors and the Endothelium
- 88 GATA Transcription Factors
- 89 Coupling: The Role of Ets Factors
- 90 Early Growth Response-1 Coupling in Vascular Endothelium
- 91 KLF2: A “Molecular Switch” Regulating Endothelial Function
- 92 NFAT Transcription Factors
- 93 Forkhead Signaling in the Endothelium
- 94 Genetics of Coronary Artery Disease and Myocardial Infarction: The MEF2 Signaling Pathway in the Endothelium
- 95 Vezf1: A Transcriptional Regulator of the Endothelium
- 96 Sox Genes: At the Heart of Endothelial Transcription
- 97 Id Proteins and Angiogenesis
- 98 Introductory Essay: Endothelial Cell Output
- 99 Proteomic Mapping of Endothelium and Vascular Targeting in Vivo
- 100 A Phage Display Perspective
- 101 Hemostasis and the Endothelium
- 102 Von Willebrand Factor
- 103 Tissue Factor Pathway Inhibitor
- 104 Tissue Factor Expression by the Endothelium
- 105 Thrombomodulin
- 106 Heparan Sulfate
- 107 Antithrombin
- 108 Protein C
- 109 Vitamin K–Dependent Anticoagulant Protein S
- 110 Nitric Oxide as an Autocrine and Paracrine Regulator of Vessel Function
- 111 Heme Oxygenase and Carbon Monoxide in Endothelial Cell Biology
- 112 Endothelial Eicosanoids
- 113 Regulation of Endothelial Barrier Responses and Permeability
- 114 Molecular Mechanisms of Leukocyte Transendothelial Cell Migration
- 115 Functions of Platelet-Endothelial Cell Adhesion Molecule-1 in the Vascular Endothelium
- 116 P-Selectin
- 117 Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1
- 118 E-Selectin
- 119 Endothelial Cell Apoptosis
- 120 Endothelial Antigen Presentation
- PART III VASCULAR BED/ORGAN STRUCTURE AND FUNCTION IN HEALTH AND DISEASE
- PART IV DIAGNOSIS AND TREATMENT
- PART V CHALLENGES AND OPPORTUNITIES
- Index
- Plate section
80 - Regulation of Angiogenesis and Vascular Remodeling by Endothelial Akt Signaling
from PART II - ENDOTHELIAL CELL AS INPUT-OUTPUT DEVICE
Published online by Cambridge University Press: 04 May 2010
Edited by
Book contents
- Frontmatter
- Contents
- Editor, Associate Editors, Artistic Consultant, and Contributors
- Preface
- PART I CONTEXT
- PART II ENDOTHELIAL CELL AS INPUT-OUTPUT DEVICE
- 27 Introductory Essay: Endothelial Cell Input
- 28 Hemodynamics in the Determination of Endothelial Phenotype and Flow Mechanotransduction
- 29 Hypoxia-Inducible Factor 1
- 30 Integrative Physiology of Endothelial Cells: Impact of Regional Metabolism on the Composition of Blood-Bathing Endothelial Cells
- 31 Tumor Necrosis Factor
- 32 Vascular Permeability Factor/Vascular Endothelial Growth Factor and Its Receptors: Evolving Paradigms in Vascular Biology and Cell Signaling
- 33 Function of Hepatocyte Growth Factor and Its Receptor c-Met in Endothelial Cells
- 34 Fibroblast Growth Factors
- 35 Transforming Growth Factor-β and the Endothelium
- 36 Thrombospondins
- 37 Neuropilins: Receptors Central to Angiogenesis and Neuronal Guidance
- 38 Vascular Functions of Eph Receptors and Ephrin Ligands
- 39 Endothelial Input from the Tie1 and Tie2 Signaling Pathway
- 40 Slits and Netrins in Vascular Patterning: Taking Cues from the Nervous System
- 41 Notch Genes: Orchestrating Endothelial Differentiation
- 42 Reactive Oxygen Species
- 43 Extracellular Nucleotides and Nucleosides as Autocrine and Paracrine Regulators within the Vasculature
- 44 Syndecans
- 45 Sphingolipids and the Endothelium
- 46 Endothelium: A Critical Detector of Lipopolysaccharide
- 47 Receptor for Advanced Glycation End-products and the Endothelium: A Path to the Complications of Diabetes and Inflammation
- 48 Complement
- 49 Kallikrein-Kinin System
- 50 Opioid Receptors in Endothelium
- 51 Snake Toxins and Endothelium
- 52 Inflammatory Cues Controlling Lymphocyte–Endothelial Interactions in Fever-Range Thermal Stress
- 53 Hyperbaric Oxygen and Endothelial Responses in Wound Healing and Ischemia–Reperfusion Injury
- 54 Barotrauma
- 55 Endothelium and Diving
- 56 Exercise and the Endothelium
- 57 The Endothelium at High Altitude
- 58 Endothelium in Space
- 59 Toxicology and the Endothelium
- 60 Pericyte–Endothelial Interactions
- 61 Vascular Smooth Muscle Cells: The Muscle behind Vascular Biology
- 62 Cross-Talk between the Red Blood Cell and the Endothelium: Nitric Oxide as a Paracrine and Endocrine Regulator of Vascular Tone
- 63 Leukocyte–Endothelial Cell Interactions
- 64 Platelet–Endothelial Interactions
- 65 Cardiomyocyte–Endothelial Cell Interactions
- 66 Interactions between Hepatocytes and Liver Sinusoidal Endothelial Cells
- 67 Stellate Cell–Endothelial Cell Interactions
- 68 Podocyte–Endothelial Interactions
- 69 Introductory Essay: Endothelial Cell Coupling
- 70 Endothelial and Epithelial Cells: General Principles of Selective Vectorial Transport
- 71 Electron Microscopic–Facilitated Understanding of Endothelial Cell Biology: Contributions Established during the 1950s and 1960s
- 72 Weibel-Palade Bodies: Vesicular Trafficking on the Vascular Highways
- 73 Multiple Functions and Clinical Uses of Caveolae in Endothelium
- 74 Endothelial Structures Involved in Vascular Permeability
- 75 Endothelial Luminal Glycocalyx: Protective Barrier between Endothelial Cells and Flowing Blood
- 76 The Endothelial Cytoskeleton
- 77 Endothelial Cell Integrins
- 78 Aquaporin Water Channels and the Endothelium
- 79 Ion Channels in Vascular Endothelium
- 80 Regulation of Angiogenesis and Vascular Remodeling by Endothelial Akt Signaling
- 81 Mitogen-Activated Protein Kinases
- 82 Protein Kinase C
- 83 Rho GTP-Binding Proteins
- 84 Protein Tyrosine Phosphatases
- 85 Role of β-Catenin in Endothelial Cell Function
- 86 Nuclear Factor-κB Signaling in Endothelium
- 87 Peroxisome Proliferator-Activated Receptors and the Endothelium
- 88 GATA Transcription Factors
- 89 Coupling: The Role of Ets Factors
- 90 Early Growth Response-1 Coupling in Vascular Endothelium
- 91 KLF2: A “Molecular Switch” Regulating Endothelial Function
- 92 NFAT Transcription Factors
- 93 Forkhead Signaling in the Endothelium
- 94 Genetics of Coronary Artery Disease and Myocardial Infarction: The MEF2 Signaling Pathway in the Endothelium
- 95 Vezf1: A Transcriptional Regulator of the Endothelium
- 96 Sox Genes: At the Heart of Endothelial Transcription
- 97 Id Proteins and Angiogenesis
- 98 Introductory Essay: Endothelial Cell Output
- 99 Proteomic Mapping of Endothelium and Vascular Targeting in Vivo
- 100 A Phage Display Perspective
- 101 Hemostasis and the Endothelium
- 102 Von Willebrand Factor
- 103 Tissue Factor Pathway Inhibitor
- 104 Tissue Factor Expression by the Endothelium
- 105 Thrombomodulin
- 106 Heparan Sulfate
- 107 Antithrombin
- 108 Protein C
- 109 Vitamin K–Dependent Anticoagulant Protein S
- 110 Nitric Oxide as an Autocrine and Paracrine Regulator of Vessel Function
- 111 Heme Oxygenase and Carbon Monoxide in Endothelial Cell Biology
- 112 Endothelial Eicosanoids
- 113 Regulation of Endothelial Barrier Responses and Permeability
- 114 Molecular Mechanisms of Leukocyte Transendothelial Cell Migration
- 115 Functions of Platelet-Endothelial Cell Adhesion Molecule-1 in the Vascular Endothelium
- 116 P-Selectin
- 117 Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1
- 118 E-Selectin
- 119 Endothelial Cell Apoptosis
- 120 Endothelial Antigen Presentation
- PART III VASCULAR BED/ORGAN STRUCTURE AND FUNCTION IN HEALTH AND DISEASE
- PART IV DIAGNOSIS AND TREATMENT
- PART V CHALLENGES AND OPPORTUNITIES
- Index
- Plate section
Summary
Since the initial identification of several classes of receptor tyrosine kinases and their ligands as crucial mediators of vascular development, considerable progress has been made toward understanding the process of angiogenesis at sites of tissue growth and/or repair (1,2). A number of clinical trials are currently evaluating angiogenic ligands for their ability to induce neovascularization in ischemic tissues (3,4), and the intracellular signaling pathways that mediate the proangiogenic effects of these growth factors are being extensively investigated. Among a number of signaling pathways activated by angiogenic growth factors, the phosphoinositide 3-kinase (PI3K)/Akt pathway is of particular interest because it regulates downstream target molecules that are potentially involved in blood vessel growth and homeostasis, and thus seems to be a major mediator that couples “inputs” with “outputs” in the endothelium.
PI3K-AKT SIGNALING AXIS: UPSTREAM ACTIVATORS AND DOWNSTREAM TARGETS
Akt originally was identified as a cellular counterpart of the oncogene derived from the murine AKT8 retrovirus; the same gene product was independently isolated as a protein kinase related to protein kinase A and C and was therefore named protein kinase B (PKB) or RAC (related to protein kinase A and C) (5–8). Mammalian genomes contain three Akt genes, Akt1/PKBα, Akt2/PKBβ, and Akt3/PKBγ, whereas Drosophila melanogaster and Caenorhabditis elegans contain one and two Akt genes, respectively (9,10). These genes encode proteins containing a pleckstrin homology (PH) domain in the amino terminus, a central kinase domain, and a carboxy terminal regulatory domain.
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- Endothelial Biomedicine , pp. 729 - 736Publisher: Cambridge University PressPrint publication year: 2007