An agent-based model of leukocyte transendothelial migration during atherogenesis
Authored by Rita Bhui, Heather N Hayenga
Date Published: 2017
DOI: 10.1371/journal.pcbi.1005523
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Abstract
A vast amount of work has been dedicated to the effects of hemodynamics
and cytokines on leukocyte adhesion and trans-endothelial migration
(TEM) and subsequent accumulation of leukocyte-derived foam cells in the
artery wall. However, a comprehensive mechanobiological model to capture
these spatiotemporal events and predict the growth and remodeling of an
atherosclerotic artery is still lacking. Here, we present a multiscale
model of leukocyte TEM and plaque evolution in the left anterior
descending (LAD) coronary artery. The approach integrates cellular
behaviors via agent-based modeling (ABM) and hemodynamic effects via
computational fluid dynamics (CFD). In this computational framework, the
ABM implements the diffusion kinetics of key biological proteins, namely
Low Density Lipoprotein (LDL), Tissue Necrosis Factor alpha (TNF-alpha),
Interlukin-10 (IL-10) and Interlukin-1 beta (IL-1 beta), to predict
chemotactic driven leukocyte migration into and within the artery wall.
The ABM also considers wall shear stress (WSS) dependent leukocyte TEM
and compensatory arterial remodeling obeying Glagov's phenomenon.
Interestingly, using fully developed steady blood flow does not result
in a representative number of leukocyte TEM as compared to pulsatile
flow, whereas passing WSS at peak systole of the pulsatile flow waveform
does. Moreover, using the model, we have found leukocyte TEM increases
monotonically with decreases in luminal volume. At critical plaque
shapes the WSS changes rapidly resulting in sudden increases in
leukocyte TEM suggesting lumen volumes that will give rise to rapid
plaque growth rates if left untreated. Overall this multi-scale and
multi-physics approach appropriately captures and integrates the
spatiotemporal events occurring at the cellular level in order to
predict leukocyte transmigration and plaque evolution.
Tags
Endothelial-cells
Tumor-necrosis-factor
Factor-alpha
Wall shear-stress
Coronary-artery-disease
Polymorphonuclear leukocytes
Vascular endothelium
Proinflammatory cytokines
Intravascular ultrasound
Atherosclerotic plaque