PCSK9 Human
Description
PCSK9 Human Recombinant produced in HEK cells is a single, glycosylated, polypeptide chain (Gln31-Gln692) containing a total of 672 amino acids, having a calculated molecular mass of 72.4kDa and fused to a 10 aa His tag at C-Terminus.
Product Specs
Product Science Overview
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a protein that plays a crucial role in cholesterol metabolism. It has garnered significant attention due to its potential as a therapeutic target for lowering low-density lipoprotein cholesterol (LDL-C) levels. This article delves into the background, discovery, and therapeutic implications of PCSK9.
PCSK9 was first identified in 2003 by Abifadel et al. during their study of French individuals with autosomal dominant hypercholesterolemia who did not have mutations in the canonical familial hypercholesterolemia genes, such as the LDL receptor (LDLR) and apolipoprotein B100 (APOB) . It was later discovered that these individuals had a gain-of-function mutation in PCSK9, which is now understood to be a key regulator in cholesterol homeostasis .
PCSK9 is produced and secreted by hepatocytes (liver cells). Once in the extracellular milieu, PCSK9 binds to the LDL receptor (LDLR) on the surface of cells and promotes its degradation . This process reduces the number of LDLRs available to clear LDL-C from the bloodstream, leading to higher levels of LDL-C .
The discovery of PCSK9’s role in cholesterol metabolism opened new avenues for therapeutic intervention. Gain-of-function mutations in PCSK9 lead to elevated LDL-C levels, while loss-of-function mutations result in lower LDL-C levels . This understanding led researchers to explore the potential of inhibiting PCSK9 as a means to lower LDL-C levels.
Inhibition of PCSK9 is achieved through monoclonal antibodies that prevent PCSK9 from binding to LDLR, thereby increasing the number of LDLRs available to clear LDL-C from the bloodstream . Clinical trials have shown that this approach is safe and highly effective in lowering LDL-C levels in patients with hypercholesterolemia, including those with familial hypercholesterolemia .
PCSK9 inhibitors have been shown to significantly reduce LDL-C levels and, consequently, the risk of cardiovascular events in patients with high cholesterol . The European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) recommend the use of PCSK9 inhibitors in patients who do not achieve their LDL-C goals with statins and ezetimibe .
