VASCULAR ENDOTHELIAL GROWTH FACTOR ACTIVITY DYNAMICS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们对基于光的治疗的微血管反应的理解还处于起步阶段。 关于该响应的大部分已知信息来自组织光学的计算建模和啮齿动物微血管的短期（<24 h）监测。 最近，我们已经证明，慢性微血管对光损伤的反应可以与建模或短期体内实验预测的有很大不同。 具体来说，我们已经观察到一个强大的微血管修复过程，导致微血管网络对光治疗的弹性比以前预测的更强。 我们和其他研究人员已经证明了使用抗血管生成剂来调节微血管对光治疗的反应并增强靶向微血管的持续血管关闭的潜力。 这些初步结果产生了很大的兴奋，可能使用这种组合的光/药物为基础的协议，以提高光动力治疗癌症和激光治疗的葡萄酒色斑胎记。 然而，这种联合方法的疗效在很大程度上取决于两种疗法的适当安排，目前尚不清楚。 为了解决这个问题，有必要了解生化因素在整个微血管修复过程中的作用。 有了这些信息，将有可能解决以下基本的未回答的问题：什么是基因表达，局部氧合和结构重建的微血管系统后，基于光的治疗之间的关系？ 抗血管生成剂如何调节这些因子和整体修复反应？ 该项目的目标是定量地绘制血流、组织氧合和血管内皮生长因子（VEGF）活性对光损伤的体内动力学。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.