Agent‐based computational model of retinal angiogenesis simulates microvascular network morphology as a function of pericyte coverage

Objective Define a role for perivascular cells during developmental retinal angiogenesis in the context of EC Notch1‐DLL4 signaling at the multicellular network level. Methods The retinal vasculature is highly sensitive to growth factor‐mediated intercellular signaling. Although EC signaling has bee...

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Vydáno v:	Microcirculation (New York, N.Y. 1994) Ročník 24; číslo 8
Hlavní autoři:	Walpole, Joseph, Mac Gabhann, Feilim, Peirce, Shayn M, Chappell, John C
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Wiley Subscription Services, Inc 01.11.2017
Témata:	agent‐based model Angiogenesis Animals Computer Simulation endothelial cell Intracellular Signaling Peptides and Proteins - metabolism Male Membrane Proteins - metabolism Mice Microcirculation - physiology Models, Cardiovascular Neovascularization, Physiologic pericyte Pericytes - metabolism Receptor, Notch1 - metabolism retina Retina - metabolism Retinal Vessels - physiology Signal Transduction - physiology agent-based model pericyte retina angiogenesis endothelial cell
ISSN:	1073-9688, 1549-8719, 1549-8719
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Shrnutí:	Objective Define a role for perivascular cells during developmental retinal angiogenesis in the context of EC Notch1‐DLL4 signaling at the multicellular network level. Methods The retinal vasculature is highly sensitive to growth factor‐mediated intercellular signaling. Although EC signaling has been explored in detail, it remains unclear how PC function to modulate these signals that lead to a diverse set of vascular network patterns in health and disease. We have developed an ABM of retinal angiogenesis that incorporates both ECs and PCs to investigate the formation of vascular network patterns as a function of pericyte coverage. We use our model to test the hypothesis that PC modulate Notch1‐DLL4 signaling in endothelial cell‐endothelial cell interactions. Results Agent‐based model (ABM) simulations that include PCs more accurately predict experimentally observed vascular network morphologies than simulations that lack PCs, suggesting that PCs may influence sprouting behaviors through physical blockade of endothelial intercellular connections. Conclusions This study supports a role for PCs as a physical buffer to signal propagation during vascular network formation—a barrier that may be important for generating healthy microvascular network patterns.
Bibliografie:	Funding information American Heart Association (13PRE16580001), National Institutes of Health (T32‐HL007284, 1R01EY022063, 1R00HL105779), National Science Foundation (1235244), The Hartwell Foundation ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1073-9688 1549-8719 1549-8719
DOI:	10.1111/micc.12393