VASCULAR ENDOTHELIAL GROWTH FACTOR ACTIVITY DYNAMICS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our understanding of the microvascular response to light-based therapy is in its infancy. Much of what is known about the response is derived from computational modeling of tissue optics and short-term (<24 h) monitoring of rodent microvasculature. Recently, we have demonstrated that the chronic microvascular response to light-based injury can differ substantially from that predicted with modeling or from short-term in vivo experiments. Specifically, we have observed a robust microvascular repair process, resulting in a stronger resiliency of the microvascular network to light-based therapy than previously predicted. We and other investigators have demonstrated the potential of using antiangiogenic agents to modulate the microvascular response to light-based therapy and enhance persistent vascular shutdown of the targeted microvasculature. These preliminary results have generated a great deal of excitement for the possible use of this combined light-/drug-based protocol to enhance photodynamic therapy of cancer and laser therapy of port wine stain birthmarks. However, the efficacy of this combined method is strongly dependent on the appropriate scheduling of the two therapies, which currently is unknown. To address this problem, it is necessary to understand the role of biochemical factors in the overall microvascular repair process. With such information, it will become possible to address the following fundamental unanswered questions: What is the relationship between gene expression, local oxygenation, and structural remodeling of the microvasculature after light-based therapy? How do antiangiogenic agents modulate these factors and the overall repair response? The goal of this project is to map quantitatively the in vivo dynamics of blood flow, tissue oxygenation, and vascular endothelial growth factor (VEGF) activity to light-based injury.