This volume addresses current emerging concepts in the field of angiogenesis, including important angiogenesis modifiers which are essential in combination with growth factors (VEGF and FGF) for the physiological process and also for therapeutic applications. It covers many of the lesser discussed areas including blood vessel growth guidance (interactions with CNS) as well as emerging practical applications of these concepts. The book comprises in-depth reviews by leading experts in several major areas: recent basic science discoveries about angiogenesis modifiers (semaphorins, ephrins and nitric oxide, for which the Nobel Prize was awarded); arterial guidance; clinical applications of new angiogenic factors (HGF, HIF and eNOS); and basic and clinical advancement of anti-angiogenic molecules for the treatment of cancer and macular degeneration (tyrosine kinase inhibitors and NO). These topics, especially their unique combination presented in this volume, are not found in any other current books on angiogenesis. This makes the book a must-read for readers both interested and actively involved in the most recent advances in basic principles and clinical applications of angiogenesis.

lgli/_393528.3824299e534fb87505ea4336ec17165f.pdf

lgrsnf/_393528.3824299e534fb87505ea4336ec17165f.pdf

zlib/Medicine/Michael Simons, Gabor M. Rubanyi/Modern Concepts in Angiogenesis_1102134.pdf

Cardiac Fibrillation-defibrillation: Clinical And Engineering Aspects Clinical and Engineering Aspects

edited by Michael Simons, Gabor M. Rubanyi

Simons, Michael; Rubanyi, Gabor M

World Scientific Publishing Company

United Kingdom and Ireland, United Kingdom

London, Hackensack, NJ, England, 2007

London, Hackensack, NJ, c2007

July 26, 2007

2, 20070726

до 2011-08

lg663191

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Includes bibliographical references and index.

I Components of Angiogenic Cascades......Page 6
Contributors......Page 14
Preface......Page 20
1. Introduction and Historical Perspective......Page 24
2. The Semaphorins......Page 26
3. The Plexin Receptor Family......Page 27
4. The Neuropilins......Page 29
5. Vascular Endothelial Growth Factors and Their Receptors......Page 31
6. Signal Transduction by Neuropilins......Page 34
7. The Role of the Neuropilins in the Regulation of Vasculogenesis and Angiogenesis......Page 37
References......Page 40
1. Introduction......Page 50
1.1. Eph receptor domain structure......Page 51
1.2. The ephrin domain structure......Page 52
1.3. Eph-Ephrin bidirectional signaling at sites of cell-to-cell contact......Page 53
2.1. Ephrin-A1 and EphA2......Page 55
2.2. Ephrin-A1 and EphA4......Page 57
2.3.1. EphB forward signaling......Page 58
2.3.2. Ephrin-B reverse signaling......Page 60
2.4. Crosstalk with other angiogenic pathways......Page 62
3. Endothelial Cell Fate......Page 65
4.1. Ephrin-A1 and EphA receptors......Page 66
4.2. EphB4 and Ephrin-B2......Page 67
4.3. Other EphB receptors and Ephrin-Bs......Page 71
5. Lymphatic Vessels......Page 72
6.1. Quiescent vasculature......Page 73
6.2. Physiological angiogenesis......Page 74
6.4. Tumor angiogenesis......Page 75
6.4.1. Ephrin-A1 and EphA2......Page 77
6.4.2. Ephrin-B2 and EphB4......Page 79
7. Targeting Eph Receptor-Ephrin Interactions to Modulate Angiogenesis......Page 81
8. Perspectives......Page 82
References......Page 83
1. Introduction......Page 90
2. Molecular Mechanisms......Page 91
3. Role in Vascular Development......Page 96
4. FGFs in Tumor Angiogenesis......Page 98
6. Role in Repair-Associated Angiogenesis and Ischemia Revascularization......Page 101
7. Conclusion......Page 103
References......Page 104
1. The NPY System......Page 114
2. NPY as a Growth Factor for Vascular Cells......Page 116
3. DPPIV: A Molecular Switch of the NPY Angiogenic System......Page 120
4. Downstream Mediators of NPY Actions......Page 121
5. NPY in Revascularization of Ischemic Tissues......Page 122
6. NPY in Wound Healing......Page 124
7. NPY in Adipose Tissue Growth and Obesity......Page 125
8. NPY in Retinopathy......Page 126
10. NPY in Tumor Angiogenesis......Page 128
11. NPY-Mediated Angiogenesis and Neurogenesis......Page 132
References......Page 134
1. Introduction......Page 142
2. Historical Perspective......Page 144
3.1. The HSPG core proteins......Page 146
3.2. The structure of the HS chain......Page 147
3.3. The biosynthesis of HS......Page 149
3.4. The post-synthetic processing of HSPGs......Page 151
4. Evolution of HSPGs......Page 152
5. HSPGs in Development......Page 154
6.1. HSPGs are co-receptors that augment ternary complex formation......Page 156
6.2. HSPG co-receptors confer unique regulatory properties......Page 157
6.2.1. Co-receptors engender stoichiometric control of signaling......Page 159
6.2.3. HS sequence motifs regulate signaling......Page 160
8. Future Therapeutic Directions......Page 162
9. Conclusions......Page 163
References......Page 164
II Angiogenic Regulators......Page 8
1. Introduction: Blood Vessels and Nerves Use Similar Guidance Cues......Page 170
2. Semaphorin Signaling......Page 171
2.1. Neuropilins......Page 173
2.2. Plexins......Page 174
3. Ephrins and Eph Signaling......Page 179
3.1. Forward signaling......Page 181
3.2. Reverse signaling......Page 183
4. Netrin and Slit Signaling......Page 186
5. Open Questions......Page 188
References......Page 189
1. Oxygen Homeostasis: Phylogeny, Ontogeny, Physiology, and Pathobiology......Page 198
2. Hypoxia-Inducible Factor 1: Master Regulator of O2 Homeostasis......Page 201
3. Control of Angiogenic Growth Factor and Cytokine Production by HIF-1......Page 207
4. Cell-Autonomous Effects of HIF-1 in Vascular Endothelial Cells......Page 208
5. Control of Angiogenesis and Arteriogenesis by HIF-1......Page 209
6. Control of Tumor Angiogenesis by HIF-1......Page 221
References......Page 227
1. Introduction......Page 240
2. Reactive Oxygen Species (ROS) in the Vasculature......Page 241
3. ROS and Angiogenesis......Page 242
4. NAD(P)H Oxidase: A Major Source of ROS in the Vasculature......Page 245
5. Role of NAD(P)H Oxidase in Angiogenesis......Page 248
6. ROS as Signaling Molecules in Angiogenesis......Page 252
7. Angiogenesis-Dependent Transcription Factors and Genes Regulated by ROS......Page 256
References......Page 258
1. Introduction......Page 276
3. Pressure Overload-Induced Hypertrophy......Page 277
4. Volume Overload-Induced Cardiac Hypertrophy......Page 281
5. Thyroxine-Induced Hypertrophy......Page 283
6. Hypoxia-Induced Hypertrophy......Page 284
7. Exercise-Induced Hypertrophy......Page 286
8. Myocardial Infarction-Induced Hypertrophy......Page 287
9. Modulators of Angiogenesis During Hypertrophy......Page 290
10. Stimuli of Angiogenesis During Hypertrophy......Page 292
11. Summary......Page 294
References......Page 295
1. Introduction......Page 304
2. Coronary Resistance......Page 306
3.1. Intrinsic and extrinsic vasomotor control......Page 308
3.2. Role of the endothelium......Page 310
3.4. Flow-induced dilation......Page 315
3.5. Neurohumoral influence on microcirculation......Page 317
3.6. Intrinsic myogenic tone......Page 319
3.7. Impact of extravascular and humoral factors on the coronary microcirculation......Page 320
3.8. Role of venules in coronary resistance......Page 322
4. Endothelial Factors in Vascular Growth and Response to Injury......Page 323
5. Impact of Disease States on Coronary Circulation......Page 324
6. The Coronary Microcirculation in Hypertophic States......Page 328
7. Summary......Page 329
References......Page 330
III Clinical Applications......Page 11
1. Kinase Inhibition and Tumor Angiogenesis......Page 336
2.1. VEGF signaling......Page 337
4. Need for Selectivity of Anti-Angiogenic Kinase Inhibitors......Page 338
5. Kinase Inhibitors in Clinical Development......Page 339
5.2. PTK/ZK (Vatalanib)......Page 349
5.3. SU11248 (Sunitinib)......Page 350
5.4. ZD6474......Page 351
5.6. AEE788......Page 352
5.10. Chir-258......Page 353
5.12. SU5416 (Semaxinib)......Page 354
6. Challenges and Future Directions......Page 355
References......Page 358
1. Introduction......Page 366
2. Concepts and Rationales......Page 367
3. Strategy......Page 369
4.1. Growth factor-based, angiogenic approach......Page 371
4.2. Cell therapy-based, vasculogenic and paracrine approach......Page 374
5.1. Choice of biological agent......Page 375
5.2. Pharmacokinetics and delivery mode......Page 377
5.3. Monitoring of neovascularization......Page 379
5.4. Study design......Page 380
6. Emerging Concepts of Therapeutic Angiogenesis......Page 381
6.1. Neovascularization responsiveness......Page 382
7. Future Prospective......Page 384
References......Page 386
1. Hepatocyte Growth Factor in Cardiovascular System......Page 390
2. HGF Signaling in Endothelial Cells......Page 391
3. Angiogenic Therapy for Ischemic Peripheral Arterial Diseases......Page 393
4. Clinical Trial in PAD......Page 394
5. HGF Gene Therapy for Myocardial Ischemia......Page 398
6. HGF Gene Therapy for Restenosis After Angioplasty......Page 400
7. Next Five Years Perspective — Future Direction of HGF Therapy......Page 401
Acknowledgments......Page 402
References......Page 403
1.1. Nitric oxide synthases......Page 408
1.2. Physiological role of endothelial NO (“EDNO”)......Page 409
1.3. Endothelial NO-deficiency in cardiovascular diseases......Page 410
1.4. Therapeutic restoration of endothelial NO production in cardiovascular diseases......Page 411
2.1. VEGF causes endothelium-dependent vasodilation mediated by EDNO......Page 412
2.2. Tumor angiogenesis and NO......Page 413
2.4. Role of NO in post-ischemic revascularization......Page 414
2.6. Molecular mechanisms......Page 415
3.1. Gene delivery vectors......Page 416
3.3. NOS-II gene transfer......Page 417
4.1. Impaired angiogenesis and arteriogenesis in patients with critical limb ischemia......Page 418
4.2.1. NOS-III-KO mice......Page 419
4.2.2. NOS-III transgenic mice......Page 420
4.2.3. Wild-type NOS-III gene transfer in normal rats......Page 422
4.3. Impaired post-ischemic flow recovery is age dependent in NOS-III-KO mice......Page 423
4.4. Advantages of a constitutively more active and “risk factor-resistant” mutant NOS-III gene......Page 424
4.5.1. Plasmid delivery of the NOS1177D gene......Page 426
4.5.2. Adenoviral delivery of the NOS1179D gene......Page 427
4.5.3. Effect of NOS1177D gene transfer in mouse CLI models without genetic deficiency of NOS-III......Page 429
5.1. Facilitation of coronary angiogenesis and ischemia-induced collateral growth......Page 430
5.2. NOS-III-derived nitric oxide facilitate myocardial gene transfer by adenoviral vectors......Page 432
6. Conclusions......Page 433
References......Page 434
Index......Page 446

This volume addresses current emerging concepts in the field of angiogenesis, including important angiogenesis modifiers which are essential in combination with growth factors (VEGF and FGF) for the physiological process and also for therapeutic applications. It covers many of the lesser discussed areas including blood vessel growth guidance (interactions with CNS) as well as emerging practical applications of these concepts. The book comprises in-depth reviews by leading experts in several major areas: recent basic science discoveries about angiogenesis modifiers (semaphorins, ephrins and nitric oxide, for which the Nobel Prize was awarded); arterial guidance; clinical applications of new angiogenic factors (HGF HIF and NOS); and basic and clinical advancement of anti-angiogenic molecules for the treatment of cancer and macular degeneration (tyrosine kinase inhibitors, endostatin and NO). These topics, especially their unique combination presented in this volume, are not found in any other current books on angiogenesis. This makes the book a must-read for readers both interested and actively involved in the most recent advances in basic principles and clinical applications of angiogenesis

2011-08-31