Affiliation:
1. Functional Endoproteolysis Laboratory, Montreal Clinical Research Institute, Montreal, H2W 1R7 QC, Canada
Abstract
Proprotein Convertase Subtilisin/Kexin-type 9 (PCSK9) is a circulating negative regulator of hepatic low-density lipoprotein receptor (LDLR), which clears cholesterol from blood. Gain-of-function genetic mutations that amplify PCSK9 activity have been found to cause potentially lethal familial hypercholesterolemia. Inversely, reduction of its activity through loss-of-function genetics or with pharmaceuticals was shown to increase hepatic LDLR, to lower blood cholesterol, and to protect against cardiovascular diseases. New epidemiological and experimental evidence suggests that this reduction could also attenuate inflammation, reinforce cancer immunity, provide resistance to infections, and protect against liver pathologies. In this review, we question the relevance of this protein under normal physiology. We propose that PCSK9 is an important, but nonessential, modulator of cholesterol metabolism and immunity, and that its pathogenicity results from its chronic overexpression.
Funder
Aclon Foundation
Richard and Edith Strauss Foundation
Fondation J-Louis Levesque
Foundation Notre Dame De Zeitoun
Publisher
Canadian Science Publishing
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
3 articles.
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