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Published in: Basic Research in Cardiology 2/2015

Open Access 01-03-2015 | Invited Review

Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9)

Authors: Rainer Schulz, Klaus-Dieter Schlüter, Ulrich Laufs

Published in: Basic Research in Cardiology | Issue 2/2015

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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.
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Metadata
Title
Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9)
Authors
Rainer Schulz
Klaus-Dieter Schlüter
Ulrich Laufs
Publication date
01-03-2015
Publisher
Springer Berlin Heidelberg
Published in
Basic Research in Cardiology / Issue 2/2015
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI
https://doi.org/10.1007/s00395-015-0463-z

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