Genetics of Angiogenesis

Book Cover......Page 1
Half-Title......Page 2
Title......Page 3
Copyright......Page 4
Contents......Page 5
Contributors......Page 9
Preface......Page 11
1. Introduction......Page 13
2.3 Arteries versus veins......Page 14
3. Vascular bed-specific VEGF signaling......Page 16
4. Lymphatic vessels versus systemic vessels......Page 17
6.1 Primary pulmonary hypertension......Page 18
6.2 Hereditary telangiectasia......Page 19
6.3 Hemangiomas......Page 20
7. Summary......Page 21
References......Page 22
1. Introduction......Page 29
2.1 Structure and functional domains of Eph receptors......Page 30
2.2 Cellular responses to Eph receptor signaling......Page 33
2.3 Cross-talk of Eph receptors with other signaling pathways......Page 35
3.2 Ephrin-A reverse signaling......Page 37
3.3 Reverse signaling by ephrin-B proteins......Page 38
4. Eph/ephrins in the cardiovascular system......Page 40
4.2 The role ofEphB receptors and ephrinB ligands in vascular development......Page 41
4.3 Eph/ephrin-mediated interactions between endothelial cells and other tissues......Page 43
4.4 Arterial-venous identity......Page 45
5. Roles for Eph receptors and ephrins in cancer?......Page 47
References......Page 48
1.1 Isolation and structure of angiopoietin-1......Page 57
1.4 Microvascular development and vessel integrity......Page 59
1.5 Recruitment of pericytes......Page 60
1.7 Cell survival......Page 61
1.8 Sprouting and branching in vitro and in vivo......Page 62
1.11 Vascular polarity......Page 63
2.2 Regulators of Ang2 expression......Page 64
2.3 Proposed biologic roles of Ang2......Page 66
4. Summary......Page 68
References......Page 69
1. Introduction......Page 72
2. Expression and possible involvement of the ETS family of transcription factors in embryonic vascular development......Page 73
2.2 FLI-1 (Friend leukemia int integration-site 1)......Page 74
3. Role of ETS-1 in postnatal angiogenesis......Page 75
3.2 Effect of hypoxia on the expression of ETS-1......Page 76
3.3 Role of ETS-1 in angiogenesis......Page 77
3.4 Target genes of ETS-1 in ECs......Page 78
3.5 Regulation of ETS-1 activity......Page 79
4. ETS-1 and endothelial apoptosis......Page 80
References......Page 81
1. Introduction......Page 86
2. VEGF isoforms resulting from alternative splicing......Page 87
2.3 Differential expression and functions of the isoforms......Page 88
3.1 Rapid degradation of the VEGF mRNA......Page 90
3.2 Stabilization of VEGFmRNA: Cis-elements and trans-acting factors......Page 91
4. Alternative polyadenylation sites......Page 92
5.1 Translation of the VEGF mRNA can occur by internal ribosome entry......Page 93
5.2 Location of the VEGF IRES within the 5’UTR......Page 94
5.4 Utilization of alternative start codons......Page 95
References......Page 96
2.1 Adaptive response to low O2 (hypoxia)......Page 102
2.2 HIF-1 is a master regulator of hypoxia......Page 103
2.3 O2 sensing pathway......Page 104
3.1 HIF function is required for vessel development......Page 105
3.2 Molecular mechanism of HIF-mediated embryonic angiogenesis......Page 106
3.3 Evolution conservation between vessel development in mammal and tracheal formation in Drosophila......Page 107
4.2 HIF pathway regulating tumor angiogenesis in animal models......Page 108
4.3 Frequent deregulation of HIF pathway in human malignancies......Page 110
References......Page 112
1. Introduction......Page 119
2. Zebrafish as a model organism to study vascular development......Page 120
3.1 1nitial specification of angioblasts......Page 123
3.2 Vasculogenesis......Page 125
3.3 Angiogenesis......Page 128
4. Angiogenesis as a stress response and its potential use......Page 130
5. Summary and perspectives......Page 132
References......Page 133
1. Introduction......Page 138
2. Structure and vasculature of mouse skin......Page 139
3. Approaches to study blood vessels in mouse skin......Page 140
4. Molecular approaches to skin transgenics......Page 141
4.1 Constitutive skin expression systems......Page 142
4.2 Inducible skin expression systems......Page 144
5.1 VEGF-A......Page 152
5.2 Angiopoietin-1......Page 153
5.4 Hypoxia inducible factor......Page 154
5.5 Lymphatic growth factors—VEGF-C, VEGF-C165S, soluble VEGF-R3......Page 155
5.8 TGF-b1......Page 156
6. Transgenic mice with skin carcinogenesis and angiogenesis......Page 157
6.2 c-myc oncogene......Page 158
7. Discussion......Page 159
References......Page 160
1. Introduction......Page 167
1.1 Insights from vasculogenesis and angiogenesis......Page 168
3.1 Venous malformations and blue rubber bleb nevus syndrome/bean syndrome......Page 169
4. Malformations resulting from transforming growth factor (TGF)-β superfamily dysfunction......Page 170
4.1 Arteriovenous malformations and hereditary hemorrhagic telangiectasia......Page 172
4.2 Pulmonary arterial abnormalities in primary pulmonary hypertension (PPH)......Page 174
4.3 The overlap between PPH and HHT......Page 175
5.1 Capillary venous malformations (cerebral cavernous angiomas/malformations, CCM): defective ras or integrin signaling?......Page 176
5.3 Arterial malformations in neurofibromatosis type I......Page 177
6. Overlaps and perspectives......Page 178
References......Page 179
1. Introduction......Page 186
2.1 Vasculogenesis......Page 189
2.2 Embryonic angiogenesis......Page 193
3. The genetic program for adult angiogenesis......Page 194
4. Comparison of genetic programs for embryonic vascular development and adult angiogenesis......Page 195
References......Page 197
1.1 What is the vascular map?......Page 201
2. Evidence for vascular heterogeneity......Page 202
4. In vivo phage display......Page 203
5. Data derived from mouse models and relevance to human vascular biology......Page 204
6. In vivo phage display screening in humans......Page 205
References......Page 207
1. Introduction......Page 211
2.1 Differing molecular pathways to angiogenesis......Page 213
2.2 Neovascularization......Page 214
3.1 Genes of angiogenesis......Page 217
3.3 Genome-scale gene expression......Page 219
4.1 Balance model of angiogenesis......Page 221
5. Conclusions......Page 222
References......Page 223
Index......Page 232