Angiogenesis induced by mast cell secretion in rat peritoneal connective tissue is a process of three phases

In the present study methods for morphometric evaluation of angiogenesis in the mesenteric window model were developed and used to assess kinetics of angiogenesis induced by either ip saline or the mast cell secretagogue 48/80. Morphometric variables included vessel density (VD), vessel luminal diameter (VLD), vessel luminal surface area (VSA), vessel luminal volume (VLV), vascularized area (VA), and number of circumferential vessels (CV). The kinetic pattern induced by 48/80 consisted of three phases. The first phase was characterized by a pronounced increase of CV, VD, VSA, and VLV and a decrease of VLD on Day 9. The second protracted phase (Day 9 to Day 37) was characterized by a continuing increase of VA together with remodeling of the vascular network (decrease of CV, VD, VSA, VLV and normalization of VLD). In the third phase (Days 37-65) no further expansion of the vascular network was present. Following saline injections ip, the characteristic kinetic pattern was a transient initial expansion of the vessel trees with significant increases of CV, VSA, and VLV on Day 9, while VD and VLD were unchanged, followed by a continuous regression. The results, including a protracted distinguishing second angiogenesis phase after 48/80 injections, strongly argues against short-lived mediators released from mast cells as decisive for the process but rather indicate that other factors, possibly related to macrophage infiltration are important.