Aggregated LDL in contact with macrophages induces local increases in free cholesterol levels that regulate local actin polymerization
Grosheva I et al. – Results describe a novel process during aggregated LDL (agLDL)–macrophage interactions in which local release of free cholesterol causes local actin polymerization, promoting a pathological positive feedback loop for increased catabolism of agLDL and eventual foam cell formation. Methods- Study of whether engagement of agLDL by macrophages leads to local increases in free cholesterol levels and whether these increases in free cholesterol regulate signals that control cellular actin
Results- AgLDL resides for prolonged periods in surface-connected compartments
- agLDL remains extracellular
- An increase in free cholesterol occurs at sites of contact between agLDL and cells due to hydrolysis of agLDL-derived cholesteryl ester
- Increased free cholesterol causes enhanced actin polymerization around agLDL
- Inhibition of cholesteryl ester hydrolysis results in decreased actin polymerization
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