PCSK9: A Potential Therapeutic Target for Sepsis

Figure 1

Roles of PCSK9 in the cholesterol metabolism and inhibitors in the hepatocytes, adipocyte, and macrophages. PCSK9 in the hepatocytes was catalyzed in the endoplasmic reticulum, followed by secretion to the peripheral parts. Finally, it led to escorting LDL-C and LDL-R to lysosome for degradation. The PCSK9 siRNA and the antibody could trigger the decline of PCSK9 amount in the intracellular and extracellular regions. VLDL-R sequesters lipopolysaccharide into adipose tissue during sepsis, while PCSK9 could downregulate the number of VLDL-R in the adipocytes, which then affected the uptake of LPS by the adipose tissues. The PCSK9 could activate the inflammation through the TLR4-activated NF-κB signaling pathway. Some of the PCSK9 inhibitors were in clinical trials or on the market, including anti-PCSK9 antibody and siRNA.