- •CONTENTS
- •Contributors
- •Preface
- •I Components of Angiogenic Cascades
- •1. Introduction and Historical Perspective
- •2. The Semaphorins
- •3. The Plexin Receptor Family
- •4. The Neuropilins
- •5. Vascular Endothelial Growth Factors and Their Receptors
- •6. Signal Transduction by Neuropilins
- •7. The Role of the Neuropilins in the Regulation of Vasculogenesis and Angiogenesis
- •8. Modulation of Angiogenesis by Semaphorins that Bind Directly to Plexins
- •Acknowledgments
- •References
- •1. Introduction
- •1.1. Eph receptor domain structure
- •1.2. The ephrin domain structure
- •2. Effects on Vascular Cell Behavior and Signaling Pathways
- •2.1. Ephrin-A1 and EphA2
- •2.2. Ephrin-A1 and EphA4
- •2.3. Ephrin-B and EphB
- •2.3.1. EphB forward signaling
- •2.3.2. Ephrin-B reverse signaling
- •2.4. Crosstalk with other angiogenic pathways
- •3. Endothelial Cell Fate
- •4. Angiogenic Remodeling of Embryonic Blood Vessels
- •4.1. Ephrin-A1 and EphA receptors
- •4.2. EphB4 and Ephrin-B2
- •4.3. Other EphB receptors and Ephrin-Bs
- •5. Lymphatic Vessels
- •6. Adult Vasculature
- •6.1. Quiescent vasculature
- •6.2. Physiological angiogenesis
- •6.3. Inflammation and wound healing
- •6.4. Tumor angiogenesis
- •6.4.1. Ephrin-A1 and EphA2
- •6.4.2. Ephrin-B2 and EphB4
- •8. Perspectives
- •Acknowledgments
- •References
- •1. Introduction
- •2. Molecular Mechanisms
- •3. Role in Vascular Development
- •4. FGFs in Tumor Angiogenesis
- •5. Role of FGFs in Developmental and Tumor Lymphangiogenesis
- •7. Conclusion
- •Acknowledgments
- •References
- •1. The NPY System
- •2. NPY as a Growth Factor for Vascular Cells
- •3. DPPIV: A Molecular Switch of the NPY Angiogenic System
- •4. Downstream Mediators of NPY Actions
- •5. NPY in Revascularization of Ischemic Tissues
- •6. NPY in Wound Healing
- •7. NPY in Adipose Tissue Growth and Obesity
- •8. NPY in Retinopathy
- •10. NPY in Tumor Angiogenesis
- •11. NPY-Mediated Angiogenesis and Neurogenesis
- •References
- •1. Introduction
- •2. Historical Perspective
- •3.1. The HSPG core proteins
- •3.2. The structure of the HS chain
- •3.3. The biosynthesis of HS
- •3.4. The post-synthetic processing of HSPGs
- •4. Evolution of HSPGs
- •5. HSPGs in Development
- •6. HSPG Modulation of Ligand-Receptor Interactions
- •6.2. HSPG co-receptors confer unique regulatory properties
- •6.2.1. Co-receptors engender stoichiometric control of signaling
- •6.2.2. The effects of glycanation
- •6.2.3. HS sequence motifs regulate signaling
- •7. HSPGs Enable Global Control of EC Phenotype
- •8. Future Therapeutic Directions
- •9. Conclusions
- •References
- •II Angiogenic Regulators
- •1. Introduction: Blood Vessels and Nerves Use Similar Guidance Cues
- •2. Semaphorin Signaling
- •2.1. Neuropilins
- •2.2. Plexins
- •3. Ephrins and Eph Signaling
- •3.1. Forward signaling
- •3.2. Reverse signaling
- •4. Netrin and Slit Signaling
- •5. Open Questions
- •References
- •1. Oxygen Homeostasis: Phylogeny, Ontogeny, Physiology, and Pathobiology
- •5. Control of Angiogenesis and Arteriogenesis by HIF-1
- •6. Control of Tumor Angiogenesis by HIF-1
- •References
- •1. Introduction
- •2. Reactive Oxygen Species (ROS) in the Vasculature
- •3. ROS and Angiogenesis
- •4. NAD(P)H Oxidase: A Major Source of ROS in the Vasculature
- •5. Role of NAD(P)H Oxidase in Angiogenesis
- •6. ROS as Signaling Molecules in Angiogenesis
- •8. Conclusion
- •References
- •1. Introduction
- •2. Assessing Coronary Angiogenesis and Arteriogenesis
- •3. Pressure Overload-Induced Hypertrophy
- •4. Volume Overload-Induced Cardiac Hypertrophy
- •5. Thyroxine-Induced Hypertrophy
- •6. Hypoxia-Induced Hypertrophy
- •7. Exercise-Induced Hypertrophy
- •8. Myocardial Infarction-Induced Hypertrophy
- •9. Modulators of Angiogenesis During Hypertrophy
- •10. Stimuli of Angiogenesis During Hypertrophy
- •11. Summary
- •References
- •1. Introduction
- •2. Coronary Resistance
- •3. Regulation of Coronary Microvascular Tone
- •3.1. Intrinsic and extrinsic vasomotor control
- •3.2. Role of the endothelium
- •3.3. Role of metabolism and autoregulation
- •3.4. Flow-induced dilation
- •3.5. Neurohumoral influence on microcirculation
- •3.6. Intrinsic myogenic tone
- •3.7. Impact of extravascular and humoral factors on the coronary microcirculation
- •3.8. Role of venules in coronary resistance
- •4. Endothelial Factors in Vascular Growth and Response to Injury
- •5. Impact of Disease States on Coronary Circulation
- •6. The Coronary Microcirculation in Hypertophic States
- •7. Summary
- •References
- •III Clinical Applications
- •1. Kinase Inhibition and Tumor Angiogenesis
- •2. Major Angiogenesis Factors and Receptors
- •2.1. VEGF signaling
- •3. Further Angiogenesis-Related Signaling
- •4. Need for Selectivity of Anti-Angiogenic Kinase Inhibitors
- •5. Kinase Inhibitors in Clinical Development
- •5.1. BAY 43-9006 (Sorafenib)
- •5.2. PTK/ZK (Vatalanib)
- •5.3. SU11248 (Sunitinib)
- •5.9. BIBF 1120
- •5.10. Chir-258
- •5.12. SU5416 (Semaxinib)
- •6. Challenges and Future Directions
- •Acknowledgments
- •References
- •1. Introduction
- •2. Concepts and Rationales
- •3. Strategy
- •4. Clinical Trials
- •4.1. Growth factor-based, angiogenic approach
- •4.2. Cell therapy-based, vasculogenic and paracrine approach
- •5. Issues Regarding Current Strategy
- •5.1. Choice of biological agent
- •5.2. Pharmacokinetics and delivery mode
- •5.3. Monitoring of neovascularization
- •5.4. Study design
- •6. Emerging Concepts of Therapeutic Angiogenesis
- •6.1. Neovascularization responsiveness
- •6.2. Genetic determination of neovascularization
- •7. Future Prospective
- •8. Summary
- •References
- •1. Hepatocyte Growth Factor in Cardiovascular System
- •2. HGF Signaling in Endothelial Cells
- •3. Angiogenic Therapy for Ischemic Peripheral Arterial Diseases
- •4. Clinical Trial in PAD
- •5. HGF Gene Therapy for Myocardial Ischemia
- •6. HGF Gene Therapy for Restenosis After Angioplasty
- •7. Next Five Years Perspective — Future Direction of HGF Therapy
- •Acknowledgments
- •References
- •1. Endothelial Nitric Oxide in Health and Disease
- •1.1. Nitric oxide synthases
- •1.2. Physiological role of endothelial NO (“EDNO”)
- •1.3. Endothelial NO-deficiency in cardiovascular diseases
- •1.4. Therapeutic restoration of endothelial NO production in cardiovascular diseases
- •2. Nitric Oxide and Angiogenesis
- •2.2. Tumor angiogenesis and NO
- •2.3. Evidence in cultured endothelial cells and in rabbit cornea
- •2.4. Role of NO in post-ischemic revascularization
- •2.6. Molecular mechanisms
- •3. NOS Gene Transfer
- •3.1. Gene delivery vectors
- •3.2. NOS-III gene transfer
- •3.3. NOS-II gene transfer
- •4.1. Impaired angiogenesis and arteriogenesis in patients with critical limb ischemia
- •4.2.1. NOS-III-KO mice
- •4.2.2. NOS-III transgenic mice
- •4.2.3. Wild-type NOS-III gene transfer in normal rats
- •4.5.1. Plasmid delivery of the NOS1177D gene
- •4.5.2. Adenoviral delivery of the NOS1179D gene
- •6. Conclusions
- •Acknowledgments
- •References
- •Index
CONTRIBUTORS
R. Wayne Alexander
Division of Cardiology, Department of Medicine
Emory University School of Medicine
1639 Pierce Drive
Atlanta, GA, 30322, USA
Patrick Auguste
Molecular Angiogenesis Laboratory INSERM EMI 0113
Université Bordeaux I Avenue des Facultés 33 405 Talence, France
Andreas Bikfalvi
Molecular Angiogenesis Laboratory INSERM EMI 0113
Université Bordeaux I Avenue des Facultés 33 405 Talence, France
Munir Boodhwani
Division of Cardiothoracic Surgery, Department of Surgery
Beth Israel-Deaconess Medical Center
Harvard Medical School
110 Francis St., LMOB 2a
Boston, MA 02215, USA
xiii
xiv Contributors
Andreas Chlistalla
Medical Development-Oncology, Schering AG
Muellerstraße 178
D-13342, Berlin, Germany
Eduard I. Dedkov
Department of Anatomy and Cell Biology
and the Cardiovascular Center
Carver College of Medicine
University of Iowa
Iowa City, IA 52242, USA
Arie Horowitz
Angiogenesis Research Centre and
Section of Cardiology, Department of Medicine
Dartmouth Medical School
Borwell Building 554W, One Medical Center Drive
Lebanon, NH 03756, USA
Ofra Kessler
Cancer and Vascular Biology Research Center
Rappaport Research Institute in the Medical Sciences
The Bruce Rappaport Faculty of Medicine
Technion, Israel Institute of Technology
1 Efron St., P.O. Box 9679
Haifa, 31096, Israel
Joanna B. Kitlinska
Department of Physiology and Biophysics
Georgetown University Medical Center
3900 Reservoir Dr, NW
Washington, DC 20057, USA
Contributors xv
Tali Lange
Cancer and Vascular Biology Research Center
Rappaport Research Institute in the Medical Sciences
The Bruce Rappaport Faculty of Medicine
Technion, Israel Institute of Technology
1 Efron St., P.O. Box 9679
Haifa, 31096, Israel
Ryuichi Morishita
Division of Clinical Gene Therapy
Osaka University Graduate School of Medicine
2-2 Yamada-oka, Suita 565-0871, Japan
Masahiro Murakami
Angiogenesis Research Centre and
Section of Cardiology, Department of Medicine
Dartmouth Medical School
Borwell Building 554W, One Medical Center Drive
Lebanon, NH 03756, USA
Gera Neufeld
Cancer and Vascular Biology Research Center
Rappaport Research Institute in the Medical Sciences
The Bruce Rappaport Faculty of Medicine
Technion, Israel Institute of Technology
1 Efron St., P.O. Box 9679
Haifa, 31096, Israel
Toshio Ogihara
Department of Geriatric Medicine
Osaka University Graduate School of Medicine
2-2 Yamada-oka, Suita 565-0871, Japan
xvi Contributors
Elena B. Pasquale
The Burnham Institute for Medical Research 10901 N. Torrey Pines Rd.
La Jolla, CA 92037, USA
and Pathology Department University of California San Diego La Jolla, CA 92093, USA
Basel Ramlawi
Division of Cardiothoracic Surgery, Department of Surgery
Beth Israel-Deaconess Medical Center
Harvard Medical School
110 Francis St., LMOB 2a
Boston, MA 02215, USA
Gabor M. Rubanyi
Chief Scientific Officer
Cardium Therapeutics
3611 Valley Center Drive, Suite 525
San Diego, CA 92130, USA
Frank W. Sellke
Division of Cardiothoracic Surgery, Department of Surgery
Beth Israel-Deaconess Medical Center
Harvard Medical School
110 Francis St., LMOB 2a
Boston, MA 02215, USA
Gregg L. Semenza
Vascular Biology Program, Institute for Cell Engineering Departments of Pediatrics, Medicine, Oncology,
and Radiation Oncology
McKusick-Nathans Institute of Genetic Medicine The Johns Hopkins University School of Medicine Broadway Research Building, Suite 671
Contributors xvii
733 North Broadway
Baltimore, MD 21205, USA
Niva Shraga-Heled
Cancer and Vascular Biology Research Center
Rappaport Research Institute in the Medical Sciences
The Bruce Rappaport Faculty of Medicine
Technion, Israel Institute of Technology
1 Efron St., P.O. Box 9679
Haifa, 31096, Israel
Nicholas W. Shworak
Section of Cardiology, Department of Medicine
Dartmouth Medical School and
Angiogenesis Research Center
HB7504, Dartmouth-Hitchcock Medical Center
Borwell Building 540W, One Medical Center Drive
Lebanon, NH 03756, USA
Michael Simons
Section of Cardiology, Department of Medicine
Dartmouth Medical School and
Angiogenesis Research Centre
Borwell Building 554W, One Medical Center Drive
Lebanon, NH 03756, USA
Karl-Heinz Thierauch
Global Research Business Area-Oncology, Schering AG
Muellerstraße 178
D-13342, Berlin, Germany
Robert J. Tomanek
Department of Anatomy and Cell Biology
and the Cardiovascular Center
1-402 BSB, Carver College of Medicine
University of Iowa
Iowa City, IA 52242, USA
xviii Contributors
Masuko Ushio-Fukai
Division of Cardiology, Department of Medicine
Emory University School of Medicine
1639 Pierce Drive, Rm. 319
Atlanta, GA, 30322, USA
Zofia Zukowska
Department of Physiology and Biophysics
Georgetown University Medical Center
Box 571460
3900 Reservoir Dr, NW
Washington, DC 20057, USA
