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Motivation: 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-/- 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. Results: We describe a large-scale mechanistic, mathematical model of atherosclerosis in the Apoe-/- mouse and its validation with in vivo Apoe -/- 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 in vivo experiments and paves the way for a similar modeling approach for human disease. Availability: The model is available by remote desktop client at Apoe.entelos.com.
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Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.