Gene set enrichment analysis reveals several globally affected pathways due to SKI-1/S1P inhibition in HepG2 cells.

Sterol regulatory element-binding proteins (SREBPs) are transcription factors governing transcription of genes related to cholesterol and fatty acid metabolism. To become active, SREBPs must undergo a proteolytic cleavage to allow an active NH(2)-terminal segment to translocate into the nucleus. SKI-1/S1P is the first protease in the proteolytic activation cascade of SREBPs.

Secreted apolipoprotein E reduces macrophage-mediated LDL oxidation in an isoform-dependent way.

As an inflammatory cell, the macrophage produces various oxidizing agents, such as free radical species. These can modify LDL as a secondary effect and doing so may favor atherogenic processes. Any molecule able to counteract these reactions would be of much benefit, especially if secreted by the macrophage itself at the lesion site.