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Blood flow can signal during angiogenesis not only through mechanotransduction, but also by affecting growth factor distribution

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Abstract

Growth factors, such as VEGF, promote the sprouting of new blood vessels. Growth factors are generally produced far from the endothelium, and the transport of these proteins is often assumed to occur through diffusion. When sprouting occurs in a perfused vascular bed, however, interstitial flow is present that can modify protein transport. We recently developed a technique to analyze flow dynamics and vascular remodeling simultaneously in avian embryos. In this study, we extend our technique to model interstitial flow through the porous matrix of the mesenchymal tissue and use this to investigate how flow in the blood vessels affects the distribution of growth factors in the mesenchyme, using VEGF as a prototypical angiogenic molecule. We find that flow controls sprouting location and elongation, both through the direct action of mechanical force and through indirect effects on growth factor distribution. Most importantly, we find that the distribution of VEGF is regulated by interstitial flow, and the effect of diffusion of VEGF is negligible.

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Funding

EAVJ was supported by a grant from Life Science Research Partners and a grant from the C1 Internal funding program of KU Leuven. RLL was supported by grants from Canadian Institute of Health Research (MOP-119292). SG was supported by a McGill Engineering Doctoral Awards. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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SG designed experiments, performed experiments, wrote and designed computational code, and analyzed the data. RL designed computational code and analyzed data. EAVJ designed experiments, performed experiments, and analyzed the data.

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Correspondence to Elizabeth A. V. Jones.

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The authors have no conflicting financial, personal, or professional interests that could be construed as influencing the work.

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Ghaffari, S., Leask, R.L. & Jones, E.A.V. Blood flow can signal during angiogenesis not only through mechanotransduction, but also by affecting growth factor distribution. Angiogenesis 20, 373–384 (2017). https://doi.org/10.1007/s10456-017-9553-x

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