title: Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9).
abstract: The proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising treatment target to lower serum cholesterol, a major risk factor of cardiovascular diseases. Gain-of-function mutations of PCSK9 are associated with hypercholesterolemia and increased risk of cardiovascular events. Conversely, loss-of-function mutations cause low-plasma LDL-C levels and a reduction of cardiovascular risk without known unwanted effects on individual health. Experimental studies have revealed that PCSK9 reduces the hepatic uptake of LDL-C by increasing the endosomal and lysosomal degradation of LDL receptors (LDLR). A number of clinical studies have demonstrated that inhibition of PCSK9 alone and in addition to statins potently reduces serum LDL-C concentrations. This review summarizes the current data on the regulation of PCSK9, its molecular function in lipid homeostasis and the emerging evidence on the extra-hepatic effects of PCSK9.
authors.affiliation: Physiologisches Institut, Justus-Liebig Universität Giessen, Aulweg 129, 35392, Giessen, Germany, Rainer.schulz@physiologie.med.uni-giessen.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Schlüter
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D006706:Homeostasis; D006801:Humans; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000502:physiology*; D012697:Serine Endopeptidases / Q000502:physiology*
chemical_list: C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases