title: Blood flow can signal during angiogenesis not only through mechanotransduction, but also by affecting growth factor distribution.
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.
authors.affiliation: Department of Chemical Engineering, McGill University, 3610 University St., Montreal, QC, H3A 0C5, Canada.
authors.forename: Siavash
authors.initials: S
authors.lastname: Ghaffari
authors.affiliation: Department of Chemical Engineering, McGill University, 3610 University St., Montreal, QC, H3A 0C5, Canada.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Leask
authors.affiliation: Department of Chemical Engineering, McGill University, 3610 University St., Montreal, QC, H3A 0C5, Canada. liz.jones@kuleuven.be.|Department of Cardiovascular Sciences, KU Leuven, UZ Herestraat 49, Box 911, 3000, Louvain, Belgium. liz.jones@kuleuven.be.|Centre for Molecular and Vascular Biology, KU Leuven, UZ Herestraat 49, Box 911, 3000, Louvain, Belgium. liz.jones@kuleuven.be.
authors.forename: Elizabeth A V
authors.identifier: http://orcid.org/0000-0002-2006-7064
authors.initials: EAV
authors.lastname: Jones
mesh_terms: D000818:Animals; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013314:Stress, Mechanical; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Hemodynamics; Interstitial flow; Mechanotransduction; Vascular development