Medical Photonics Group, Institute of Bioengineering, Swiss Federal Institute of Technology (EPFL), Station 6, 1015 Lausanne, Switzerland.
Angiogenesis. 2010 Dec;13(4):281-92. doi: 10.1007/s10456-010-9185-x. Epub 2010 Sep 15.
Photodynamic therapy (PDT) induces damage to the endothelium, which can lead to increased vascular permeability and, under intensive PDT conditions, even to platelet aggregation, vasoconstriction, and blood flow stasis. Eventually, ischemia, hypoxia, and inflammation can occur, resulting in angiogenesis. We studied the sequence of the vascular events after Visudyne-PDT in the chicken chorioallantoic membrane (CAM) at day 11 of development. Using epi-fluorescence microscopy, we monitored the regrowth of capillaries in the PDT treated area. Immediately after irradiation, the treatment resulted in blood flow arrest. And 24 h post PDT, sprouting of new blood vessels was observed at the edge of the PDT zone. Neovessels looping out from the edge of the PDT zone gave rise to specialized endothelial tip structures guiding the vessels towards the center of the treated area. At 48 h almost all of the treated area was repopulated with functional but morphologically altered vasculature. These observations also showed reperfusion of some of the vessels that had been closed by the PDT treatment. CAM samples were immunohistochemically stained for Ki-67 showing proliferation of endothelial cells in the PDT area. Also, several markers of immature and angiogenic blood vessels, such as αVβ3-integrin, vimentin and galectin-1, were found to be enhanced in the PDT area, while the endothelial maturation marker intercellular adhesion molecule (ICAM)-1 was found to be suppressed. These results demonstrate that the new vascular bed is formed by both neo-angiogenesis and reperfusion of existing vessels. Both the quantitative real-time RT-PCR profile and the response to pharmacological treatment with Avastin, an inhibitor of angiogenesis, suggest that angiogenesis occurs after PDT. The observed molecular profiling results and the kinetics of gene regulation may enable optimizing combination therapies involving PDT for treatment of cancer and other diseases.
光动力疗法（PDT）会损伤血管内皮，导致血管通透性增加，在强烈的 PDT 条件下甚至会导致血小板聚集、血管收缩和血流停滞。最终会导致缺血、缺氧和炎症，从而引发血管生成。我们在鸡胚绒毛尿囊膜（CAM）发育第 11 天研究了 Visudyne-PDT 后血管事件的发生顺序。使用荧光显微镜，我们监测了 PDT 治疗区域内毛细血管的再生情况。照射后即刻，治疗导致血流停止。在 PDT 后 24 小时，观察到 PDT 区域边缘有新血管的发芽。从 PDT 区域边缘伸出的新血管形成专门的内皮尖端结构，引导血管向治疗区域中心生长。在 48 小时时，几乎所有的治疗区域都被具有功能但形态改变的脉管系统重新填充。这些观察结果还表明，一些被 PDT 治疗关闭的血管也出现了再灌注。CAM 样本通过 Ki-67 的免疫组织化学染色显示 PDT 区域内皮细胞的增殖。此外，还发现了一些不成熟和血管生成的血管标志物，如 αVβ3 整合素、波形蛋白和半乳糖凝集素-1，在 PDT 区域增强，而内皮成熟标志物细胞间黏附分子（ICAM）-1 则被抑制。这些结果表明，新的血管床是由新血管生成和现有血管再灌注形成的。定量实时 RT-PCR 分析和对血管生成抑制剂 Avastin 的药理治疗反应都表明，PDT 后会发生血管生成。观察到的分子谱结果和基因调控的动力学可能使优化涉及 PDT 的联合治疗成为可能，用于治疗癌症和其他疾病。
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