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微血管重构过程中动态、异质性的内皮 Tie2 表达和毛细血管血流。

Dynamic, heterogeneous endothelial Tie2 expression and capillary blood flow during microvascular remodeling.

机构信息

Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.

Department of Ophthalmology, University of Virginia, Charlottesville, VA, USA.

出版信息

Sci Rep. 2017 Aug 22;7(1):9049. doi: 10.1038/s41598-017-08982-z.

Abstract

Microvascular endothelial cell heterogeneity and its relationship to hemodynamics remains poorly understood due to a lack of sufficient methods to examine these parameters in vivo at high resolution throughout an angiogenic network. The availability of surrogate markers for functional vascular proteins, such as green fluorescent protein, enables expression in individual cells to be followed over time using confocal microscopy, while photoacoustic microscopy enables dynamic measurement of blood flow across the network with capillary-level resolution. We combined these two non-invasive imaging modalities in order to spatially and temporally analyze biochemical and biomechanical drivers of angiogenesis in murine corneal neovessels. By stimulating corneal angiogenesis with an alkali burn in Tie2-GFP fluorescent-reporter mice, we evaluated how onset of blood flow and surgically-altered blood flow affects Tie2-GFP expression. Our study establishes a novel platform for analyzing heterogeneous blood flow and fluorescent reporter protein expression across a dynamic microvascular network in an adult mammal.

摘要

由于缺乏足够的方法在体内高分辨率地检查血管生成网络中的这些参数,因此微血管内皮细胞的异质性及其与血液动力学的关系仍未得到充分理解。功能性血管蛋白(如绿色荧光蛋白)的替代标志物的出现,使得能够使用共聚焦显微镜随着时间的推移跟踪单个细胞中的表达,而光声显微镜则可以实现对网络中毛细血管水平分辨率的血流的动态测量。我们将这两种非侵入性成像方式结合起来,以便在时空上分析小鼠角膜新生血管中血管生成的生化和生物力学驱动因素。通过在 Tie2-GFP 荧光报告小鼠中用碱烧伤刺激角膜血管生成,我们评估了血流开始和手术改变的血流如何影响 Tie2-GFP 的表达。我们的研究为分析成年哺乳动物动态微血管网络中的异质血流和荧光报告蛋白表达建立了一个新的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d91e/5567377/cbcefac06f8d/41598_2017_8982_Fig1_HTML.jpg

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