A Spatially Resolved and Quantitative Model of Early Atherosclerosis

Area of Science:

• Cardiovascular Research
• Biomedical Engineering
• Immunology

Background:

• Atherosclerosis poses a significant global health burden, necessitating a deeper understanding of its inflammatory, immunological, and biomechanical underpinnings.
• Predicting the progression, stagnation, or regression of early atherosclerotic plaques is crucial for effective prevention and treatment.
• The precise biological and mechanobiological drivers of plaque stability remain incompletely understood.

Purpose of the Study:

• To develop a quantitative, spatially resolved mathematical model to understand early atherosclerosis plaque stability.
• To identify and classify regions prone to or resistant to atherosclerotic plaque progression.
• To link plaque stability to measurable in vivo factors like cholesterol concentration and wall shear stress.

Main Methods:

• Development of a mathematical model integrating Darcy's law for transmural flow and Kedem-Katchalsky equations for endothelial fluxes.
• Incorporation of a quantitative model for early plaque formation and a novel submodel for macrophage recruitment.
• Assessment of atherosclerotic plaque stability using the developed model based on in vivo inputs.

Main Results:

• The model indicates that advective flux of lipoproteins through the endothelium is a decisive factor in plaque progression.
• Advective transport within the artery wall was found to have a negligible influence on plaque stability.
• Regions with wall shear stress below approximately 20% of average exposure are identified as potential sites for progression-prone plaque development.

Conclusions:

• The study provides a novel mathematical framework for assessing atherosclerotic plaque stability.
• Low wall shear stress is identified as a critical predictor of progression-prone atherosclerotic plaque development.
• Findings can inform targeted prevention and treatment strategies for atherosclerosis.