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Unexpected roles for PCSK9 in lipid metabolism

Soutar, Anne K

Current Opinion in Lipidology: June 2011 - Volume 22 - Issue 3 - p 192–196
doi: 10.1097/MOL.0b013e32834622b5
Lipid metabolism: Edited by Jeffrey S. Cohn

Purpose of review To consider the evidence that PCSK9 has effects on lipoprotein metabolism that are in addition to its role in promoting the degradation of the LDL receptor.

Recent findings Transgenic mice expressing human PCSK9 under physiological control have recently been described. As well as the expected effects on LDL-receptor protein levels in the liver, mice expressing the gain-of-function mutant D374Y secrete more triglyceride than control mice or mice expressing wild-type PCSK9, supporting earlier suggestions that apoB synthesis is increased in hepatocytes expressing D374Y PCSK9 and that patients heterozygous for PCSK9 mutations have increased apoB synthesis. No increase in triglyceride secretion was observed in LDLR−/− mice, suggesting that the effect of PCSK9 on triglyceride secretion is to some extent independent of the LDL receptor. Other recent studies have shown an association between serum PCSK9 concentration and serum triglyceride, but care has to be taken in interpretation of these results as it has also been shown that the level of PCSK9 in human serum shows strong diurnal variation.

Summary Understanding the physiology of PCSK9 is important because this protein has become a major new target for lipid lowering therapy.

MRC Clinical Sciences Centre, Imperial College London, London, UK

Correspondence to Anne K. Soutar, PhD, Professor of Molecular Genetics, Lipoprotein Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Ducane Road, London W1N ONN, UK Tel: +44 208 383 2324; e-mail:

© 2011 Lippincott Williams & Wilkins, Inc.