The formation of blood vessels, or vascular morphogenesis, is a fundamental biological process (Figure 157.1). In fact, the cardiovascular system is the first organ that develops in the mammalian embryo. Consequently, genetic manipulation of key regulators of the angiogenic cascade often yields dramatic phenotypes that are not compatible with life and lead to early embryonic lethality. This in turn implies that the process of blood vessel formation is under strong evolutionary pressure, and that every living animal with a closed circulation that has successfully made it through embryonic development is capable of executing the angiogenic program. As such, the formation of blood vessels is a conserved, hierarchically structured process with a high degree of similarity, both molecularly as well as functionally, in such diverse species as zebrafish (1), frog (2), mouse (3,4), and man (3,4). The goals of this chapter are to discuss: (a) the history of vascular morphogenesis research, (b) the basic principles of physiological and pathological growth of blood vessels, (c) concepts of the induction and inhibition of blood vessel growth (angiogenic switch, angiogenic balance), (d) techniques and strategies to quantitatively and qualitatively assess the structural and functional status of neovasculature, and (e) established and emerging avenues for therapeutically interfering with the growth of blood vessels (antiangiogenesis, therapeutic angiogenesis). The topic of lymphangiogenesis is reviewed separately in Chapter 169.

DEFINITIONS

The term angiogenesis is widely used when referring to the process of blood vessel formation (Table 157–1). Yet, more specifically, angiogenesis denotes the formation of new capillaries from pre-existing ones (see Figure 157.1). This occurs primarily through classical sprouting angiogenesis.