Capillary network patterning during angiogenesis.

1. Although much is known of signalling events associated with angiogenesis, starting with a sprout, less is known of how an intact microvascular network is correctly formed following the initiation of sprouting. The aim of the present report is to evaluate some of the factors that could be involved in directing the patterning of the resulting microvascular bed. 2. Hypothetical 'patterning rules' are discussed and considered in the context of data obtained from studies of angiogenesis. The guidelines suggest that both tissue- and stimulus-specific regulators are involved in directing patterning. 3. Examples of 'patterned' and 'non-patterned' angiogenesis in rat mesentery are given, with evidence to support stimulus-related differences in angiogenesis patterns. 4. Skeletal muscle angiogenesis follows metabolic patterns within the muscle, as discerned through traditional histochemical evaluation. However, further examination, using confocal microscopy and new patterning assays, indicates that branching patterns differ according to stimulus. Patterning guidelines within the tissue may be important in preventing the growth of sinusoidal vessels. 5. The concept of 'angiotypes' is proposed to direct future studies towards understanding how therapeutic angiogenesis or angiostasis applications can be used to obtain correctly patterned microvascular networks. Angiogenesis via 'branching' compared with 'non-branching' angiotypes will involve different signalling pathways. Both sprouting and dividing of capillaries are found in the 'branching' angiotype, with each pattern having several subtypes that would be expected to be mediated via different signalling mechanisms.