PCSK9 and its modulation

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a newly-recognized protein, plays a key role in regulating cholesterol homeostasis. PCSK9 reduces hepatic low-density lipoprotein receptors (LDLRs) thereby increasing LDL-cholesterol (LDL-C). Recently, biologic and genetic research proposed several approaches to inhibit or reduce PCSK9 to improve lipid profile and cardiovascular performance in patients with dyslipidemia, particularly hypercholesterolemia. Of note, PCSK9 is a secreted protein under tight control by multiple modulators. Therefore, elucidating the factors that influence PCSK9 would enhance our understanding of PCSK9 and potentially day-to-day management of these patients at high cardiovascular risk. This review will focus on genetic variants, physiologic processes, pharmacologic agents and pathologic conditions related to PCSK9 in order to assess current and future therapeutic strategies targeting this molecule.