Continuous retention of apolipoprotein B-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Cholesterol is a lipid that is an essential structural component of cellular membranes as well as a precursor of numerous endogenous signaling molecules that regulate the interface between metabolism and inflammation. Recently, aggregated, crystalline cholesterol (CC) has been recognized as a prominent driver of atherogenic inflammation. The main aim of this theme is to uncover the mechanisms by which crystalline cholesterol induce inflammatory responses and to explore novel treatment strategies in atherosclerosis.

Major achievements

• Published data showing that crystalline cholesterol induced a robust complement activation in human serum revealed by activation products from the alternative and terminal pathways.
• Published data showing that crystalline cholesterol causes a marked and dose-dependent increase in the adhesion molecules E-selectin and ICAM-1 on the surface of the endothelial cells after incubation with whole blood.
• Demonstrated that rHDL binds to crystalline cholesterol and inhibits the crystalline cholesterol-induced complement activation as measured by soluble terminal C5b-9 formation and C3c deposition on the crystalline cholesterol surface.
• Published data showing that the NEIL3 SNP rs12645561, the TT genotype is associated with increased risk of myocardial infarction.