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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Veröffentlicht in:Microcirculation (New York, N.Y. 1994) Jg. 24; H. 8
Hauptverfasser: Walpole, Joseph, Mac Gabhann, Feilim, Peirce, Shayn M, Chappell, John C
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Wiley Subscription Services, Inc 01.11.2017
Schlagworte:
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
Online-Zugang:Volltext
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Zusammenfassung: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.
Bibliographie:Funding information
American Heart Association (13PRE16580001), National Institutes of Health (T32‐HL007284, 1R01EY022063, 1R00HL105779), National Science Foundation (1235244), The Hartwell Foundation
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ISSN:1073-9688
1549-8719
1549-8719
DOI:10.1111/micc.12393