Spatial and temporal control of angiogenesis and arterialization using focal applications of VEGF164 and Ang-1

Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908 Submitted 20 June 2003 ; accepted in final form 30 October 2003 Microvascular networks undergo patterning changes that determine and reflect functional adaptations during tissue remodeling. Alterations in network architectures are a result of complex and integrated signaling events. To understand how two growth factor signals interact to stimulate angiogenesis and arterialization, we engineered spatially directed microvascular pattern changes in vivo by using combinations of focally delivered exogenous growth factors. We implanted microdelivery beads containing recombinant vascular endothelial growth factor-164 (VEGF 164 ) and recombinant angiopoietin-1* (Ang-1*) into the dorsal subcutaneous tissue of fully anesthetized male Fischer 344 rats implanted with backpack window chambers, and we quantified vascular patterning changes by using intravital microscopy, a combination of architectural metrics, and immunohistochemistry. Focal delivery of VEGF 164 caused spatially directed increases in both the total number and the density of vessels with diameters