Principles and Therapeutic Implications of Angiogenesis Vasculogenesis and Arteriogenesis

Centre for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KULeuven, Campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium [email protected]

1 Angiogenic Disorders 158

2 Modes of Vessel Growth 160

3 Vasculogenesis 164

3.1 Endothelial Progenitors in the Embryo 164

3.2 Endothelial Progenitors in the Adult 166

3.3 The Endothelial/Haematopoietic Connection: An Emerging Theme 168

3.4 Arterial and Venous Cell Fate Specification 168

3.5 Tissue-Specific Endothelial Cell Differentiation 170

4 Angiogenesis 171

4.1 Vascular Permeability and Extracellular Matrix Degradation 171

4.2 Endothelial Budding and Sprouting 174

4.3 Vascular Lumen Formation 178

4.4 Guided Navigation of Vessels 179

4.5 Vessel Maintenance 181

5 Arteriogenesis 182

5.1 Smooth Muscle Progenitor Cells 182

5.2 Smooth Muscle Cell Recruitment, Growth and Differentiation 183

6 Therapeutic Implications 186

6.1 Potential Biomarkers for Anti-angiogenic Therapy 187

6.2 Escape from Anti-angiogenic Therapy 189

6.3 Adverse Effects of Anti-angiogenic Therapy 190

References 190

Abstract The vasculature is the first organ to arise during development. Blood vessels run through virtually every organ in the body (except the avascular cornea and the cartilage), assuring metabolic homeostasis by supplying oxygen and nutrients and removing waste products. Not surprisingly therefore, vessels are critical for organ growth in the embryo and for repair of wounded tissue in the adult. Notably, however, an imbalance in angiogenesis (the growth of blood vessels) contributes to the pathogenesis of numerous malignant, inflammatory, ischaemic, infectious and immune disorders. During the last two decades, an explosive interest in angiogenesis research has generated the necessary insights to develop the first clinically approved anti-angiogenic agents for cancer and blindness. This novel treatment is likely to change the face of medicine in the next decade, as over 500 million people worldwide are estimated to benefit from pro- or anti-angiogenesis treatment. In this following chapter, we discuss general key angiogenic mechanisms in health and disease, and highlight recent developments and perspectives of anti-angiogenic therapeutic strategies.

Keywords Angiogenesis • Vasculogenesis • Arteriogenesis • Angiogenic disorders • Vessel growth • Endothelial progenitors • Haematopoietic progenitors • Guided navigation • Anti-angiogenic therapy

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