A spatially resolved and lipid-structured model for macrophage populations in early human atherosclerotic lesions
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arXiv
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| Auteurs principaux: | , , , |
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| Format: | Preprint |
| Publié: |
2025
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| _version_ | 1866910818738634752 |
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| author | Chambers, Keith L. Myerscough, Mary R. Watson, Michael G. Byrne, Helen M. |
| author_facet | Chambers, Keith L. Myerscough, Mary R. Watson, Michael G. Byrne, Helen M. |
| contents | Atherosclerosis is a chronic inflammatory disease of the artery wall. The early stages of atherosclerosis are driven by interactions between lipids and monocyte-derived-macrophages (MDMs). The mechanisms that govern the spatial distribution of lipids and MDMs in the lesion remain poorly understood. In this paper, we develop a spatially-resolved and lipid-structured model for early atherosclerosis. The model development and analysis are guided by images of human coronary lesions by Nakashima et al. 2007. Consistent with their findings, the model predicts that lipid initially accumulates deep in the intima due to a spatially non-uniform LDL retention capacity. The model also qualitatively reproduces the global internal maxima in the Nakashima images only when the MDM mobility is sufficiently sensitive to lipid content, and MDM lifespan sufficiently insensitive. Introducing lipid content-dependence to MDM mobility and mean lifespan produced minimal impact on model behaviour at early times, but strongly impacted lesion composition at steady state. Increases to the sensitivity of MDM lifespan to lipid content yield lesions with fewer MDMs, less total lesion lipid content and reduced mean MDM infiltration depth. Increases to the sensitivity of MDM mobility to lipid content also reduces the MDM infiltration depth, but increases the proportion of lipid-laden MDMs. We find that MDM lipid content increases with spatial depth, regardless of blood LDL and HDL content. These results shed light on the mechanisms that drive spatial variation in the composition of early atherosclerotic lesions, and the role of macrophage lipid content in disease progression. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2502_05039 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | A spatially resolved and lipid-structured model for macrophage populations in early human atherosclerotic lesions Chambers, Keith L. Myerscough, Mary R. Watson, Michael G. Byrne, Helen M. Cell Behavior Atherosclerosis is a chronic inflammatory disease of the artery wall. The early stages of atherosclerosis are driven by interactions between lipids and monocyte-derived-macrophages (MDMs). The mechanisms that govern the spatial distribution of lipids and MDMs in the lesion remain poorly understood. In this paper, we develop a spatially-resolved and lipid-structured model for early atherosclerosis. The model development and analysis are guided by images of human coronary lesions by Nakashima et al. 2007. Consistent with their findings, the model predicts that lipid initially accumulates deep in the intima due to a spatially non-uniform LDL retention capacity. The model also qualitatively reproduces the global internal maxima in the Nakashima images only when the MDM mobility is sufficiently sensitive to lipid content, and MDM lifespan sufficiently insensitive. Introducing lipid content-dependence to MDM mobility and mean lifespan produced minimal impact on model behaviour at early times, but strongly impacted lesion composition at steady state. Increases to the sensitivity of MDM lifespan to lipid content yield lesions with fewer MDMs, less total lesion lipid content and reduced mean MDM infiltration depth. Increases to the sensitivity of MDM mobility to lipid content also reduces the MDM infiltration depth, but increases the proportion of lipid-laden MDMs. We find that MDM lipid content increases with spatial depth, regardless of blood LDL and HDL content. These results shed light on the mechanisms that drive spatial variation in the composition of early atherosclerotic lesions, and the role of macrophage lipid content in disease progression. |
| title | A spatially resolved and lipid-structured model for macrophage populations in early human atherosclerotic lesions |
| topic | Cell Behavior |
| url | https://arxiv.org/abs/2502.05039 |