Figure 2.

Role of PCSK9 in sepsis and inflammation. Hepatic PCSK9 expression is induced by TNFα hepatocyte nuclear factor-1α (HNF-1α) and lipopolysaccharide (LPS). Once in the plasma, PCSK9 binds to the LDL receptor facilitating LDL degradation in lysosomes, thus decreasing clearance of LDL-bound LPS. Extracellular PCSK9 also enhances the expression of pro-inflammatory markers, decreases macrophages in atheroma, and the expression of LDLR and ABCA1 in these cells. It also forms a complex with Lp(a). The intracellular function of PCSK9 in inflammation remains unknown. GNB, gram-negative bacteria; mab, monoclonal antibody.