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Updated: Jun 16, 2026
06:46
Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
Published on: June 30, 2016
A macrophage sterol-responsive network linked to atherogenesis
Lev Becker1, Sina A Gharib, Angela D Irwin
1Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Cell Metabolism
|February 10, 2010
Summary
Cholesterol accumulation in macrophages triggers a protein network linked to atherosclerosis. Targeting this network with drugs or genetic changes impacts disease development, revealing key molecular players in foam cell formation.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Cholesteryl ester accumulation in macrophages is a key early step in atherosclerosis.
- Sterol loading may promote foam cell formation and vascular disease by disrupting protein networks.
Purpose of the Study:
- To identify proteins differentially expressed in cholesterol-loaded macrophages in vivo.
- To test the hypothesis that sterol loading perturbs a network of interacting proteins.
Main Methods:
- Global proteomic analysis of cholesterol-loaded macrophages.
- Biochemical fractionation to localize sterol-responsive proteins.
- Pharmacologic interventions (statin, rosiglitazone) and genetic models (LDL receptor, apolipoprotein E deficient mice).
Main Results:
- A sterol-responsive protein network was identified, enriched in interacting proteins involved in vesicular transport.
- This network showed altered expression in response to cholesterol loading.
- Pharmacologic and genetic interventions implicated this network in atherosclerosis.
- Most sterol-responsive proteins were localized to microvesicles.
Conclusions:
- A highly integrated protein network is influenced by factors in atherogenesis.
- This network plays a significant role in cholesterol metabolism and foam cell formation.
- Microvesicles provide a physical basis for the network's function in atherosclerosis.
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