Abstract
During the early stages of angiogenesis, following stimulation of endothelial cells by vascular endothelial growth factor (VEGF), the vascular wall is breached, allowing high molecular weight proteins to leak from the vessels to the interstitial space. This hallmark of angiogenesis results in deposition of a provisional matrix, elevation of the interstitial pressure and induction of interstitial convection. Albumin, the major plasma protein appears to be an innocent bystander that is significantly affected by these changes, and thus can be used as a biomarker for vascular permeability associated with angiogenesis. Traditionally, albumin leak in superficial organs was followed by colorimetry or morphometry with the use of albumin binding vital dyes. Over the last years, the introduction of tagged-albumin that can be detected by various imaging methods, such as magnetic resonance imaging and positron emission tomography, opened new possibilities for quantitative three dimension dynamic analysis of permeability in any organ. Using these tools it is now possible to follow not only vascular permeability, but also interstitial convection and lymphatic drain. Active uptake of tagged albumin by caveolae-mediated endocytosis opens the possibility for using labeled albumin for vital staining of cells and cell tracking. This approach was used for monitoring recruitment of perivascular stroma fibroblasts associated with tumor angiogenesis.
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Acknowledgments
This work was supported by the USA NIH R01 CA75334, the DKFZ-MOST cooperational program, the Israel Science Foundation 93/07, The European Commission FP6 Integrated Project MEDITRANS, The European Commission FP7 Integrated Project ENCITE and European Research Council Advanced grant 232640-IMAGO (to MN), and by the Gurwin Foundation. Michal Neeman is incumbent of the Helen and Morris Mauerberger Chair.
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Vandoorne, K., Addadi, Y. & Neeman, M. Visualizing vascular permeability and lymphatic drainage using labeled serum albumin. Angiogenesis 13, 75–85 (2010). https://doi.org/10.1007/s10456-010-9170-4
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DOI: https://doi.org/10.1007/s10456-010-9170-4