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A Macrophage Sterol-Responsive Network Linked to Atherogenesis
- Source :
- Cell Metabolism. 11:125-135
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- SummaryCholesteryl ester accumulation by macrophages is a critical early event in atherogenesis. To test the hypothesis that sterol loading promotes foam cell formation and vascular disease by perturbing a network of interacting proteins, we used a global approach to identify proteins that are differentially expressed when macrophages are loaded with cholesterol in vivo. Our analysis revealed a sterol-responsive network that is highly enriched in proteins with known physical interactions, established roles in vesicular transport, and demonstrated atherosclerotic phenotypes in mice. Pharmacologic intervention with a statin or rosiglitazone and use of mice deficient in LDL receptor or apolipoprotein E implicated the network in atherosclerosis. Biochemical fractionation revealed that most of the sterol-responsive proteins resided in microvesicles, providing a physical basis for the network's functional and biochemical properties. These observations identify a highly integrated network of proteins whose expression is influenced by environmental, genetic, and pharmacological factors implicated in atherogenesis.
- Subjects :
- Male
Apolipoprotein E
Simvastatin
Physiology
HUMDISEASE
030204 cardiovascular system & hematology
Biology
Article
Rosiglitazone
Mice
03 medical and health sciences
chemistry.chemical_compound
Apolipoproteins E
0302 clinical medicine
Animals
Hypoglycemic Agents
Receptor
Molecular Biology
Hypolipidemic Agents
030304 developmental biology
Foam cell
0303 health sciences
Cholesterol
Macrophages
Proteins
Cell Biology
Atherosclerosis
Microvesicles
Mice, Inbred C57BL
Vesicular transport protein
Sterols
Gene Expression Regulation
Receptors, LDL
chemistry
Biochemistry
LDL receptor
Cholesteryl ester
Thiazolidinediones
lipids (amino acids, peptides, and proteins)
Foam Cells
Subjects
Details
- ISSN :
- 15504131
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cell Metabolism
- Accession number :
- edsair.doi.dedup.....27b22c09d67b1af4245981f29a72340d