Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering

© 2016 The Author. Proprotein convertase subtilisin kexin 9 (PCSK9) is a key regulator of low-density lipoprotein receptor levels and LDL-cholesterol levels. Loss-of-function mutations in PCSK9 gene are associated with hypocholesterolaemia and protection against cardiovascular disease, identifying P...

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Main Authors: Norata, Giuseppe, Tavori, H., Pirillo, A., Fazio, S., Catapano, A.
Format: Journal Article
Published: 2016
Online Access:http://hdl.handle.net/20.500.11937/55517
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author Norata, Giuseppe
Tavori, H.
Pirillo, A.
Fazio, S.
Catapano, A.
author_facet Norata, Giuseppe
Tavori, H.
Pirillo, A.
Fazio, S.
Catapano, A.
author_sort Norata, Giuseppe
building Curtin Institutional Repository
collection Online Access
description © 2016 The Author. Proprotein convertase subtilisin kexin 9 (PCSK9) is a key regulator of low-density lipoprotein receptor levels and LDL-cholesterol levels. Loss-of-function mutations in PCSK9 gene are associated with hypocholesterolaemia and protection against cardiovascular disease, identifying PCSK9 inhibition as a valid therapeutic approach to manage hypercholesterolaemia and related diseases. Although PCSK9 is expressed mainly in the liver, it is present also in other tissues and organs with specific functions, raising the question of whether a pharmacological inhibition of PCSK9 to treat hypercholesterolaemia and associated cardiovascular diseases might be helpful or deleterious in non-hepatic tissues. For example, PCSK9 is expressed in the vascular wall, in the kidneys, and in the brain, where it was proposed to play a role in development, neurocognitive process, and neuronal apoptosis. A link between PCSK9 and immunity was also proposed as both sepsis and viral infections are differentially affected in the presence or absence of PCSK9. Despite the increasing number of observations, the debate on the exact roles of PCSK9 in extrahepatic tissues is still ongoing, and as very effective drugs that inhibit PCSK9 have become available to the clinician, a better understanding of the biological roles of PCSK9 is warranted.
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spelling curtin-20.500.11937-555172017-09-13T16:09:55Z Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering Norata, Giuseppe Tavori, H. Pirillo, A. Fazio, S. Catapano, A. © 2016 The Author. Proprotein convertase subtilisin kexin 9 (PCSK9) is a key regulator of low-density lipoprotein receptor levels and LDL-cholesterol levels. Loss-of-function mutations in PCSK9 gene are associated with hypocholesterolaemia and protection against cardiovascular disease, identifying PCSK9 inhibition as a valid therapeutic approach to manage hypercholesterolaemia and related diseases. Although PCSK9 is expressed mainly in the liver, it is present also in other tissues and organs with specific functions, raising the question of whether a pharmacological inhibition of PCSK9 to treat hypercholesterolaemia and associated cardiovascular diseases might be helpful or deleterious in non-hepatic tissues. For example, PCSK9 is expressed in the vascular wall, in the kidneys, and in the brain, where it was proposed to play a role in development, neurocognitive process, and neuronal apoptosis. A link between PCSK9 and immunity was also proposed as both sepsis and viral infections are differentially affected in the presence or absence of PCSK9. Despite the increasing number of observations, the debate on the exact roles of PCSK9 in extrahepatic tissues is still ongoing, and as very effective drugs that inhibit PCSK9 have become available to the clinician, a better understanding of the biological roles of PCSK9 is warranted. 2016 Journal Article http://hdl.handle.net/20.500.11937/55517 10.1093/cvr/cvw194 unknown
spellingShingle Norata, Giuseppe
Tavori, H.
Pirillo, A.
Fazio, S.
Catapano, A.
Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering
title Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering
title_full Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering
title_fullStr Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering
title_full_unstemmed Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering
title_short Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering
title_sort biology of proprotein convertase subtilisin kexin 9: beyond low-density lipoprotein cholesterol lowering
url http://hdl.handle.net/20.500.11937/55517