A Quantitative Model of Early Atherosclerotic Plaques Parameterized Using In Vitro Experiments.

Area of Science:

• Cardiovascular Biology
• Mathematical Biology
• Immunology

Background:

• Atherosclerotic plaque development involves complex immunological, lipid, and macrophage interactions within the artery wall.
• Existing mathematical models often lack parameters derived from experimental data, limiting their clinical relevance.

Purpose of the Study:

• To develop and analyze a quantitative, data-driven mathematical model of early atherosclerotic plaque development.
• To integrate inflammatory, lipid, and macrophage dynamics using an experimental, bottom-up approach.

Main Methods:

• Developed three simpler submodels fitted to in vitro experimental data.
• Constructed a quantitative model of early plaque development from these submodels.
• Performed local sensitivity analysis and analyzed long-term model outcomes.

Main Results:

• Identified critical parameters and processes influencing plaque development through sensitivity analysis.
• Characterized the stability of model plaques based on recruitment rates of lipoproteins and macrophages.
• The model provides a framework for understanding plaque progression.

Conclusions:

• The developed model is a step towards clinically relevant mathematical tools for atherosclerosis research.
• Further experimental quantification of macrophage behavior and cholesterol dynamics is recommended for deeper insights into long-term plaque outcomes.