Cell proliferation along vascular islands during microvascular network growth

Mesenteric tissues, which allow visualization of entire microvascular networks at a single cell level, were harvested from unstimulated adult male Wistar rats and Wistar rats 3 and 10？days post angiogenesis stimulation by mast cell degranulation with compound 48/80. Tissues were immunolabeled for PECAM and BRDU. Identification of vessel lumens via injection of FITC-dextran confirmed that endothelial cell segments were disconnected from nearby patent networks. Stimulated networks displayed increases in vascular area, length density, and capillary sprouting. On day 3, the percentage of islands with at least one BRDU-positive cell increased compared to the unstimulated level and was equal to the percentage of capillary sprouts with at least one BRDU-positive cell. At day 10, the number of vascular islands per vascular area dramatically decreased compared to unstimulated and day 3 levels.These results show that vascular islands have the ability to proliferate and suggest that they are able to incorporate into the microcirculation during the initial stages of microvascular network growth.Understanding the cellular dynamics involved in microvascular network growth is critical for future development of cell-specific therapies targeted at manipulating the microcirculation during tumor growth, diabetic retinopathy, myocardial infarction and other pathological conditions. Microvascular network growth in adult tissues is largely attributed to angiogenesis defined as the growth of new vessels from pre-existing vessels. Angiogenesis is commonly associated with two modes: capillary sprouting and intussusception [1]. Capillary sprouting involves the proliferation and migration of endothelial cells from an existing vessel. Intussuception is characterized by vessel splitting via the extension of endothelial cell filapodia to form an intra-lumenal pillar and subsequent lumen division. These angiogenic dynamics account for the continued remodeling and stabilization of a network [2,3].