Figure 2.

Effect of atorvastatin on hepatocyte LDLR and PCSK9. Atorvastatin increases the activity/nuclear translocation of sterol regulatory element-binding protein-2 (SREBP-2), which is a transcription factor that activates both the LDLR and PCSK9 genes. This results in increased expression and secretion of PCSK9 protein, which binds the LDLR and targets it for lysosomal degradation. This likely prevents atorvastatin from causing as much increased LDLR protein from being present on the hepatocyte plasma membrane as might otherwise be expected.