Blood Lipoproteins Shape the Phenotype and Lipid Content of Early Atherosclerotic Lesion Macrophages: A Dual-Structured Mathematical Model

Macrophages in atherosclerotic lesions exhibit a spectrum of behaviours or phenotypes . The phenotypic distribution of monocyte-derived macrophages (MDMs), its correlation with MDM lipid content, and relation to blood lipoprotein densities are not well understood. Of particular interest is the balan...

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Bibliographic Details
Published in:Bulletin of mathematical biology Vol. 86; no. 9; p. 112
Main Authors: Chambers, Keith L., Myerscough, Mary R., Watson, Michael G., Byrne, Helen M.
Format: Journal Article
Language:English
Published: New York Springer US 01.09.2024
Springer Nature B.V
Subjects:
Arteriosclerosis
Atherosclerosis
Atherosclerosis - blood
Atherosclerosis - metabolism
Atherosclerosis - pathology
Blood
Cell Biology
Cholesterol
Computer Simulation
Cytokines
Density
Gene sequencing
Genotype & phenotype
Heterogeneity
High density lipoprotein
Humans
Immunology
Inflammation
Lesions
Life Sciences
Lipid Metabolism
Lipids
Lipoproteins
Lipoproteins - blood
Lipoproteins - metabolism
Lipoproteins, HDL - blood
Lipoproteins, HDL - metabolism
Lipoproteins, LDL - blood
Lipoproteins, LDL - metabolism
Low density lipoprotein
Macrophages
Macrophages - metabolism
Macrophages - pathology
Mathematical and Computational Biology
Mathematical Concepts
Mathematical models
Mathematics
Mathematics and Statistics
Models, Cardiovascular
Monocytes
Original
Original Article
Phenotype
Phenotypes
Subsystems
Veins & arteries
Continuum
Phenotype
Discrete
Lipid
Structured population model
Atherosclerosis
ISSN:0092-8240, 1522-9602, 1522-9602
Online Access:Get full text
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Summary:Macrophages in atherosclerotic lesions exhibit a spectrum of behaviours or phenotypes . The phenotypic distribution of monocyte-derived macrophages (MDMs), its correlation with MDM lipid content, and relation to blood lipoprotein densities are not well understood. Of particular interest is the balance between low density lipoproteins (LDL) and high density lipoproteins (HDL), which carry bad and good cholesterol respectively. To address these issues, we have developed a mathematical model for early atherosclerosis in which the MDM population is structured by phenotype and lipid content. The model admits a simpler, closed subsystem whose analysis shows how lesion composition becomes more pathological as the blood density of LDL increases relative to the HDL capacity. We use asymptotic analysis to derive a power-law relationship between MDM phenotype and lipid content at steady-state. This relationship enables us to understand why, for example, lipid-laden MDMs have a more inflammatory phenotype than lipid-poor MDMs when blood LDL lipid density greatly exceeds HDL capacity. We show further that the MDM phenotype distribution always attains a local maximum, while the lipid content distribution may be unimodal, adopt a quasi-uniform profile or decrease monotonically. Pathological lesions exhibit a local maximum in both the phenotype and lipid content MDM distributions, with the maximum at an inflammatory phenotype and near the lipid content capacity respectively. These results illustrate how macrophage heterogeneity arises in early atherosclerosis and provide a framework for future model validation through comparison with single-cell RNA sequencing data.
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ISSN:0092-8240
1522-9602
1522-9602
DOI:10.1007/s11538-024-01342-9