VASCULAR ENDOTHELIAL GROWTH FACTOR ACTIVITY DYNAMICS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们对微血管对光疗法的反应的了解还处于初级阶段。关于这一反应的大部分已知来源于组织光学的计算模型和对啮齿动物微血管的短期(24小时)监测。最近，我们已经证明，慢性微血管对光损伤的反应可能与通过建模或短期活体实验预测的结果有很大不同。具体地说，我们观察到了一个强大的微血管修复过程，导致微血管网络对光基治疗的弹性比先前预测的更强。我们和其他研究人员已经证明了使用抗血管生成药物来调节微血管对基于光的治疗的反应，并增强目标微血管系统的持续性血管关闭的潜力。这些初步结果已经引起了极大的兴奋，因为可能使用这种基于光/药物的组合方案来增强癌症的光动力疗法和对葡萄酒色斑胎记的激光疗法。然而，这种联合方法的疗效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，就有可能解决以下基本的未回答的问题：基因表达、局部氧合和光治疗后微血管结构重建之间的关系是什么？抗血管生成药物是如何调节这些因子和整体修复反应的？这个项目的目标是定量地将体内血流、组织氧合和血管内皮生长因子(VEGF)活性的动态变化与光损伤联系起来。

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.