PCSK9 proprotein convertase subtilisin/kexin type (PCSK9) protein plays an important role in LDL cholesterol
(LDL-C) metabolism, due to its role in the degradation of the LDL receptor. Preliminary clinical data of PCSK9 inhibition
are quite promising and indicate that PCSK9 inhibition may be a novel strategy for the treatment of dyslipidemia
particularly for those with refractory hypercholesterolemia, statin intolerance, or an elevated lipoprotein (a) level and
associated cardiovascular diseases. Furthermore, development of PCSK9 inhibitor is an excellent example of “bench to
bedside” concept where discovery of a genetic mutation was translated into a novel therapy to address unmet clinical
needs. Although several approaches have been attempted to inhibit PCSK9 activity including small molecules, gene
silencing and inhibitory antibodies, the most promising approach appears to be the use of monoclonal antibodies with a 50
-70% LDL cholesterol reduction on top of maximal doses of statins. In this article, we review the pharmacology of
PCSK9 and summarize findings from key clinical studies using PCSK9 inhibitors.
Keywords: Antibodies, atherosclerosis, cardiovascular disease, cholesterol, dyslipidemia, inhibitors, lipoprotein metabolism,
lipoprotein receptors, low density, proprotein convertase subtilisin/kexin type 9.
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