Targeting PCSK9 for hypercholesterolemia

Dyslipidemias are a predominant risk factor for cardiovascular disease. Biological and genetic research has led to the identification of several genes and proteins that may be pharmacologically targeted to improve lipoprotein profiles and possibly cardiovascular outcomes in patients with dyslipidemi...

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Main Authors: Norata, Giuseppe, Tibolla, G., Catapano, A.
Format: Journal Article
Published: 2014
Online Access:http://hdl.handle.net/20.500.11937/56217
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author Norata, Giuseppe
Tibolla, G.
Catapano, A.
author_facet Norata, Giuseppe
Tibolla, G.
Catapano, A.
author_sort Norata, Giuseppe
building Curtin Institutional Repository
collection Online Access
description Dyslipidemias are a predominant risk factor for cardiovascular disease. Biological and genetic research has led to the identification of several genes and proteins that may be pharmacologically targeted to improve lipoprotein profiles and possibly cardiovascular outcomes in patients with dyslipidemia. The observation that proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates the levels of circulating low-density lipoprotein C (LDL-C) by enhancing the degradation of the hepatic low-density lipoprotein receptor (LDLR) prompted the search for drugs that inhibit PCSK9 activity. Several approaches to inhibiting PCSK9 activity have been proposed; these involve inhibitory antibodies, small molecules, and gene silencing. To date, the most promising and advanced approach relates to monoclonal antibodies, which can decrease LDL cholesterol by 65-70%, even as an add-on therapy to a maximal dose of a statin. Phase III studies and large, event-driven clinical trials are ongoing and will fully address the viability and role of these drugs in clinical practice. © 2014 by Annual Reviews.
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spelling curtin-20.500.11937-562172017-09-13T16:11:01Z Targeting PCSK9 for hypercholesterolemia Norata, Giuseppe Tibolla, G. Catapano, A. Dyslipidemias are a predominant risk factor for cardiovascular disease. Biological and genetic research has led to the identification of several genes and proteins that may be pharmacologically targeted to improve lipoprotein profiles and possibly cardiovascular outcomes in patients with dyslipidemia. The observation that proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates the levels of circulating low-density lipoprotein C (LDL-C) by enhancing the degradation of the hepatic low-density lipoprotein receptor (LDLR) prompted the search for drugs that inhibit PCSK9 activity. Several approaches to inhibiting PCSK9 activity have been proposed; these involve inhibitory antibodies, small molecules, and gene silencing. To date, the most promising and advanced approach relates to monoclonal antibodies, which can decrease LDL cholesterol by 65-70%, even as an add-on therapy to a maximal dose of a statin. Phase III studies and large, event-driven clinical trials are ongoing and will fully address the viability and role of these drugs in clinical practice. © 2014 by Annual Reviews. 2014 Journal Article http://hdl.handle.net/20.500.11937/56217 10.1146/annurev-pharmtox-011613-140025 restricted
spellingShingle Norata, Giuseppe
Tibolla, G.
Catapano, A.
Targeting PCSK9 for hypercholesterolemia
title Targeting PCSK9 for hypercholesterolemia
title_full Targeting PCSK9 for hypercholesterolemia
title_fullStr Targeting PCSK9 for hypercholesterolemia
title_full_unstemmed Targeting PCSK9 for hypercholesterolemia
title_short Targeting PCSK9 for hypercholesterolemia
title_sort targeting pcsk9 for hypercholesterolemia
url http://hdl.handle.net/20.500.11937/56217