III Clinical Applications

Mechanistic Considerations

313

Karl-Heinz Thierauch and Andreas Chlistalla

1.

Kinase Inhibition and Tumor Angiogenesis

313

2.

Major Angiogenesis Factors and Receptors

314

3.

Further Angiogenesis-Related Signaling

315

4.

Need for Selectivity of Anti-Angiogenic Kinase Inhibitors

315

5.

Kinase Inhibitors in Clinical Development

316

6.

Challenges and Future Directions

332

Acknowledgments

335

References

335

Chapter 12. Therapeutic Angiogenesis — An Overview

343

Masahiro Murakami and Michael Simons

1.

Introduction

343

2.

Concepts and Rationales

344

3.

Strategy

346

4.

Clinical Trials

348

5.

Issues Regarding Current Strategy

352

6.

Emerging Concepts of Therapeutic Angiogenesis

358

7.

Future Prospective

361

8.

Summary

363

References

363

Chapter 13. Hepatocyte Growth Factor

367

Ryuichi Morishita and Toshio Ogihara

1.

Hepatocyte Growth Factor in Cardiovascular System

367

2.

HGF Signaling in Endothelial Cells

368

3.

Angiogenic Therapy for Ischemic Peripheral

Arterial Diseases

370

4.

Clinical Trial in PAD

371

5.

HGF Gene Therapy for Myocardial Ischemia

375

Contents

xi

6.

HGF Gene Therapy for Restenosis After Angioplasty

377

7.

Next Five Years Perspective — Future Direction

of HGF Therapy

378

Acknowledgments

379

References

380

Chapter 14. Role of Nitric Oxide in Adult Angiogenesis:

Therapeutic Potential of Endothelial Nitric Oxide

Synthase Gene Transfer

385

Gabor M. Rubanyi

1.

Endothelial Nitric Oxide in Health and Disease

385

2.

Nitric Oxide and Angiogenesis

389

3.

NOS Gene Transfer

393

4.

Therapeutic Angiogenesis with NOS-III Gene Transfer

for Critical Limb Ischemia

395

5.

Potential Therapeutic Utility of NOS-III Gene Transfer

in the Heart

407

6.

Conclusions

410

Acknowledgments

411

References

411

Index

423