A Multiscale Model of Leukocyte Transendothelial Migration During Atherogenesis

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dc.contributor.advisorHayenga, Heather N.
dc.creatorBhui, Rita
dc.date.accessioned2019-06-13T02:51:26Z
dc.date.available2019-06-13T02:51:26Z
dc.date.created2018-05
dc.date.issued2018-05
dc.date.submittedMay 2018
dc.date.updated2019-06-13T02:53:37Z
dc.description.abstractA vast amount of work has been dedicated to understanding the role hemodynamics and cytokines play in leukocyte adhesion, 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. In this dissertation 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 of pulsatile blood flow via computational fluid dynamics (CFD). We found that using fully developed steady blood flow does not result in a representative number of leukocyte TEM as compared to pulsatile flow, whereas passing wall shear stress (WSS) at peak systole of the pulsatile flow waveform does. Moreover, using the model, we found leukocyte TEM increases monotonically with decreases in luminal volume. Specifically, neutrophils are primary cell type entering the wall at the genesis of plaque evolution and again the lumen caliber is altered for the first time. 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.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10735.1/6583
dc.language.isoen
dc.subjectLeucocytes
dc.subjectCytokines
dc.subjectCell adhesion molecules
dc.subjectHemodynamics
dc.subjectMultiagent systems
dc.subjectComputational fluid dynamics
dc.titleA Multiscale Model of Leukocyte Transendothelial Migration During Atherogenesis
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentPhysics
thesis.degree.grantorThe University of Texas at Dallas
thesis.degree.levelDoctoral
thesis.degree.namePHD

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