A biomathematical model of atherosclerosis in mice

PLoS One. 2022 Aug 3;17(8):e0272079. doi: 10.1371/journal.pone.0272079. eCollection 2022.

Abstract

Atherosclerosis is one of the leading causes of death worldwide. Biomathematical modelling of the underlying disease and therapy processes might be a useful aid to develop and improve preventive and treatment concepts of atherosclerosis. We here propose a biomathematical model of murine atherosclerosis under different diet and treatment conditions including lipid modulating compound and antibiotics. The model is derived by translating known biological mechanisms into ordinary differential equations and by assuming appropriate response kinetics to the applied interventions. We explicitly describe the dynamics of relevant immune cells and lipid species in atherosclerotic lesions including the degree of blood vessel occlusion due to growing plaques. Unknown model parameters were determined by fitting the predictions of model simulations to time series data derived from mice experiments. Parameter fittings resulted in a good agreement of model and data for all 13 experimental scenarios considered. The model can be used to predict the outcome of alternative treatment schedules of combined antibiotic, immune modulating, and lipid lowering agents under high fat or normal diet. We conclude that we established a comprehensive biomathematical model of atherosclerosis in mice. We aim to validate the model on the basis of further experimental data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis* / etiology
  • Diet, High-Fat
  • Lipids
  • Mice
  • Mice, Knockout
  • Plaque, Atherosclerotic* / complications

Substances

  • Lipids

Grants and funding

This work was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (SYMPATH, grant numbers 01ZX1906B, 01ZX1906A). AH is participant in the BIH-Charite Advanced Clinician Scientist Pilotprogram funded by the Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. We acknowledge support from Leipzig University for Open Access Publishing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.