PCSK9mediated

PCSK9mediated refers to a biological process involving the protein proprotein convertase subtilisin/kexin type 9 (PCSK9) and its role in regulating cholesterol levels. PCSK9 is a serine protease produced by the liver. Its primary function is to bind to the low-density lipoprotein receptor (LDLR) on the surface of liver cells. When PCSK9 binds to LDLR, it promotes the degradation of the LDLR in a cellular compartment called the lysosome.

The LDLR is crucial for clearing LDL cholesterol, often referred to as "bad cholesterol," from the bloodstream. By binding to and promoting the degradation of LDLR, PCSK9 effectively reduces the number of LDLRs available on the liver cell surface. This reduction in LDLRs leads to less LDL cholesterol being removed from the circulation, resulting in higher levels of LDL cholesterol in the blood. Elevated LDL cholesterol is a known risk factor for cardiovascular disease, including heart attacks and strokes.

Conversely, inhibiting PCSK9 activity can increase the number of LDLRs on the liver cell surface. This increased number of receptors leads to enhanced clearance of LDL cholesterol from the blood, thus lowering LDL cholesterol levels. This understanding has led to the development of PCSK9 inhibitors, a class of drugs used to treat hypercholesterolemia, particularly in individuals who cannot achieve target LDL cholesterol levels with statins or who are intolerant to them. These drugs are typically monoclonal antibodies that bind to PCSK9 and prevent it from interacting with the LDLR.