HDL and plaque regression in a multiphase model of early atherosclerosis

TL;DR

This study develops a multiphase model to analyze how LDL and HDL influence early atherosclerotic plaque development, revealing conditions that lead to plaque stabilization or regression based on lipid levels.

Contribution

The paper introduces a novel free boundary multiphase model to investigate the dynamic effects of LDL and HDL on early plaque growth and regression in atherosclerosis.

Findings

Lower LDL and higher HDL levels can slow or reverse plaque growth.

Plaque stabilization occurs under low LDL and high HDL influxes.

Changes in lipid profiles have limited effects on large, established plaques.

Abstract

Atherosclerotic plaques are accumulations of cholesterol-engorged macrophages in the artery wall. Plaque growth is initiated and sustained by the deposition of low density lipoproteins (LDL) in the artery wall. 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 levels. 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.