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Updated: Jun 26, 2025
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
HDL and plaque regression in a multiphase model of early atherosclerosis
Ishraq U Ahmed1, Mary R Myerscough1
1School of Mathematics and Statistics, University of Sydney, Australia.
Insights
Lowering low-density lipoprotein (LDL) and increasing high-density lipoprotein (HDL) can stabilize or regress early atherosclerosis plaque development. However, these changes have limited impact on established plaques.
Area of Science:
- Cardiovascular Science
- Computational Biology
- Biomedical Engineering
Background:
- Atherosclerosis is an arterial disease driven by lipid accumulation and immune response.
- Low-density lipoproteins (LDL) promote plaque growth, while high-density lipoproteins (HDL) facilitate cholesterol removal.
- Understanding the interplay between LDL and HDL is crucial for managing early plaque development.
Purpose of the Study:
- To model the effects of LDL and HDL on early atherosclerosis plaque development.
- To investigate how varying LDL and HDL levels influence cholesterol accumulation, cell death, and emigration.
- To identify conditions that stabilize or promote regression of early atherosclerotic plaques.
Main Methods:
- Development of a free boundary multiphase mathematical model.
- Simulation of LDL and HDL deposition rates and their impact on macrophage cholesterol levels.
- Analysis of cell death, emigration, and efferocytosis dynamics within the plaque model.
Main Results:
- A specific LDL-HDL parameter space was identified where plaque growth stabilizes due to balanced macrophage emigration and HDL clearance.
- High HDL and low LDL influxes were shown to counteract cholesterol accumulation and cell influx.
- Changes favoring lower LDL and higher HDL significantly slowed plaque growth and induced regression in early stages.
Conclusions:
- Modulating LDL and HDL levels offers a potential strategy for managing early-stage atherosclerosis.
- The model demonstrates that early intervention with optimized LDL-HDL profiles is more effective than later interventions.
- Temporary shifts in LDL-HDL levels provide only short-term benefits in slowing plaque progression.
Abstract:
Atherosclerosis is a chronic disease of the arteries characterised by the accumulation of lipids and lipid-engorged cells in the artery wall. Early plaque growth is aggravated by the deposition of low density lipoproteins (LDL) in the wall and the subsequent immune response. High density lipoproteins (HDL) counterbalance the effects of LDL by accepting cholesterol from macrophages and removing it from the plaque. In this paper, we develop a free boundary multiphase model to investigate the effects of LDL and HDL on early plaque development. We examine how the rates of LDL and HDL deposition affect cholesterol accumulation in macrophages, and how this impacts cell death rates and emigration. We identify a region of LDL-HDL parameter space where plaque growth stabilises for low LDL and high HDL influxes, due to macrophage emigration and HDL clearance that counterbalances the influx of new cells and cholesterol. We explore how the efferocytic uptake of dead cells and the recruitment of new macrophages affect plaque development for a range of LDL and HDL influxes. Finally, we consider how changes in the LDL-HDL profile can change the course of plaque development. We show that changes towards lower LDL and higher HDL can slow plaque growth and even induce regression. We find that these changes have less effect on larger, more established plaques, and that temporary changes will only slow plaque growth in the short term.
