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Updated: Mar 24, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
HDL functionality in reverse cholesterol transport--Challenges in translating data emerging from mouse models to
Miriam Lee-Rueckert1, Joan Carles Escola-Gil2, Petri T Kovanen1
1Wihuri Research Institute, Helsinki, Finland.
Insights
High-density lipoprotein (HDL) particles remove cholesterol from lesions, aiding fecal excretion. This review compares reverse cholesterol transport in mice and humans to guide HDL-targeted therapies for atherosclerosis.
Area of Science:
- Cardiovascular Science
- Metabolic Research
- Translational Medicine
Background:
- Atherosclerosis involves LDL-cholesterol accumulation in lesions.
- Macrophages become cholesterol-loaded during atherogenesis.
- Macrophage reverse cholesterol transport (RCT) is key to preventing lesion development.
Purpose of the Study:
- To compare and critically analyze RCT mechanisms in mice and humans.
- To translate in vivo findings into practical concepts for therapy development.
- To identify strategies for preventing lesion development and promoting regression.
Main Methods:
- Review of existing literature on reverse cholesterol transport.
- Comparative analysis of RCT pathways in mouse models and human studies.
- In vivo mechanistic studies of cholesterol efflux and excretion.
Main Results:
- Significant differences exist in RCT steps between mouse models and humans.
- Mouse models offer valuable insights but require careful translation to human physiology.
- Understanding species-specific differences is crucial for effective HDL-targeted therapies.
Conclusions:
- Macrophage RCT is a critical therapeutic target for atherosclerosis.
- Translating mouse model findings to humans necessitates careful consideration of species differences.
- Further research is needed to optimize HDL-targeted therapies for cardiovascular disease prevention.
Abstract:
Whereas LDL-derived cholesterol accumulates in atherosclerotic lesions, HDL particles are thought to facilitate removal of cholesterol from the lesions back to the liver thereby promoting its fecal excretion from the body. Because generation of cholesterol-loaded macrophages is inherent to atherogenesis, studies on the mechanisms stimulating the release of cholesterol from these cells and its ultimate excretion into feces are crucial to learn how to prevent lesion development or even induce lesion regression. Modulation of this key anti-atherogenic pathway, known as the macrophage-specific reverse cholesterol transport, has been extensively studied in several mouse models with the ultimate aim of applying the emerging knowledge to humans. The present review provides a detailed comparison and critical analysis of the various steps of reverse cholesterol transport in mouse and man. We attempt to translate this in vivo complex scenario into practical concepts, which could serve as valuable tools when developing novel HDL-targeted therapies.
