Dataset Information

An agent-based model of leukocyte transendothelial migration during atherogenesis.

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-?), Interlukin-10 (IL-10) and Interlukin-1 beta (IL-1?), 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.

SUBMITTER: Bhui R

PROVIDER: S-EPMC5444619 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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An agent-based model of leukocyte transendothelial migration during atherogenesis.

Bhui Rita R Hayenga Heather N HN

PLoS computational biology 20170525 5

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 descen ...[more]

PMID: 28542193

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Project description:Gastric cancer (GC) is a prevalent cancer, which remains incurable, and therefore requires an alternative treatment method. Celecoxib is a nonsteroidal anti-inflammatory drug that targets cyclooxygenase-2, and exhibits anticancer effects. The present study aimed to investigate the anti-GC mechanism of celecoxib using bioinformatics methods. Gene expression datasets GSE56807 (GC tissues and normal gastric tissues) and GSE54657 (celecoxib-treated and non-treated human GC epithelial AGS cells) were downloaded from the Gene Expression Omnibus database. Two groups of differentially expressed genes (DEGs) were identified using limma package in R language. The criterion for GSE56807 was a false discovery rate of <0.05, while that for GSE54657 was P<0.01. Overlapping DEGs from the two datasets were screened out. Subsequently, pathway enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery software (P<0.1; gene count ?2). In addition, the protein-protein interactions (PPIs) among the overlapped DEGs were obtained based on IntAct, Database of Interacting Proteins, Biomolecular Interaction Network Database and Human Protein Reference Database. Finally, a PPI network was visualized using Cytoscape software. A total of 137 overlapped DEGs were obtained, and DEGs with opposite regulation directions in the two datasets were significantly enriched in focal adhesion and leukocyte transendothelial migration. Subsequently, a PPI network of overlapped DEGs was constructed. Comprehensively, a total of 8 key DEGs [cysteine and glycine rich protein 1 (CSRP1), thrombospondin 1 (THBS1), myosin light chain 9 (MYL9), filamin A (FLNA), actinin alpha 1 (ACTN1), vinculin (VCL), laminin subunit gamma 2 (LAMC2) and claudin 1 (CLDN1)] were upregulated in GC tissues and downregulated in celecoxib-treated cells. In conclusion, celecoxib may exhibit anti-GC effects by suppressing the expression of CSRP1, THBS1, MYL9, FLNA, ACTN1, VCL, LAMC2 and CLDN1, and inhibiting leukocyte transendothelial migration and focal adhesion. However, relevant experiments are required to confirm the conclusion of the present study.

Dataset Information

An agent-based model of leukocyte transendothelial migration during atherogenesis.

Publications

An agent-based model of leukocyte transendothelial migration during atherogenesis.

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