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

Sponsors: No sponsors listed

Platforms: No platforms listed

Model Documentation: Other Narrative

Model Code URLs: Model code not found

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