Proproteine convertase subtilisin/kexin 9 or PCSK9 is a serine protease which is synthesized by the liver and released in circulation. It binds to hepatic LDL receptors which internalize inside cells where they are degraded. Thus, PCSK9 decreases the number of LDL receptors on the surface of hepatocytes, reducing the uptake of cholesterol of which concentration rises in blood. The inactivation of PCSK9 has the opposite effect, it increases the number of LDL receptors and induces a lowering the level of LDL cholesterol in blood because of an increase in its hepatic uptake. PSSK9 is in fact a regulator of the number of LDL receptors in the liver.
A clinical trial published in the NEJM of March 22nd, 2012 shows that an antibody to PSCK9 called REGN727, administered by intravenous or subcutaneous route to people with hypercholesterolemia already treated by atorvastatin, considerably reduced their LDL cholesterol level. This is a preliminary interesting result obtained through a new mechanism of action, but is not sufficient to guarantee the introduction of REGN727 in therapeutics.
Notice : Statins also act by increasing hepatic uptake of blood cholesterol by LDL receptors.
