The Apoe-/- Mouse PhysioLab® Platform: A Validated Physiologically-based Mathematical Model of Atherosclerotic Plaque Progression in the Apoe-/- Mouse

By

Chan, Jason
Vuillaume, Gregory
Bever, Caitlin
Lebrun, Stefan
Lietz, Michael
Steffen, Yvonne
Stolle, Katrin
Wahba, Karim
Wang, Xiao
Moodie, Shonna
Hoeng, Julia
Peitsch, Manuel
Powell, Lyn

Type

Article

Date of Publication

2012-9-30

Original Publication

Nature conservation

Volume

3

Pages

1--13

Subjects

Apoe-/- mouse , atherosclerosis , Cigarette smoke , Mathematical model

Contributed by

Pensoft Publishers

Language

English

Published by

Sofia, Bulgaria Pensoft Publishers 2012-

Identifiers

DOI: https://doi.org/10.7750/BioDiscovery.2012.3.2

 

Abstract

<em>Motivation:</em>Atherosclerosis is a complex multi-pathway inflammatory disease where accumulation of oxidatively modified lipids and leukocytes in the arterial intima leads to plaque formation over time. Translating Apoe<sup>-/-</sup> mouse results to the clinical setting is complicated by uncertainty around (a) mechanisms underlying disease etiology, (b) relative importance of these mechanisms as drivers of progression, and (c) how these roles change in response to perturbation by therapeutic intervention or lifestyle changes. <br><em>Results: </em>We describe a large-scale mechanistic, mathematical model of atherosclerosis in the Apoe<sup>-/-</sup> mouse and its validation with <em>in vivo</em> Apoe <sup>-/-</sup> data. Major physiological components include cholesterol/macrophage trafficking, inflammation, endothelial function, oxidative stress, and thrombosis. Heterogeneity in disease progression, observed despite genetic uniformity and experimentally controlled conditions, was captured through “virtual mice”. This model may be used to optimize <em>in vivo</em> experiments and paves the way for a similar modeling approach for human disease.<br><em>Availability: </em>The model is available by remote desktop client at Apoe.entelos.com.