PCSK9 as an Atherothrombotic Risk Factor

Disturbances in lipid metabolism are among the most important risk factors for atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein in lipid metabolism that is also involved in the production of inflammatory cytokines, endothelial dysfunction...

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Main Authors: Tadeja Sotler, Miran Šebeštjen
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/3/1966
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author Tadeja Sotler
Miran Šebeštjen
author_facet Tadeja Sotler
Miran Šebeštjen
author_sort Tadeja Sotler
collection DOAJ
description Disturbances in lipid metabolism are among the most important risk factors for atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein in lipid metabolism that is also involved in the production of inflammatory cytokines, endothelial dysfunction and aherosclerotic plaque development. Studies have shown a connection between PCSK9 and various indicators of inflammation. Signalling pathways that include PCSK9 play important role in the initiation and development of atherosclerotic lesions by inducing vascular inflammation. Studies so far have suggested that PCSK9 is associated with procoagulation, enhancing the development of atherosclerosis. Experimentally, it was also found that an increased concentration of PCSK9 significantly accelerated the apoptosis of endothelial cells and reduced endothelial function, which created conditions for the development of atherosclerosis. PCSK9 inhibitors can therefore improve clinical outcomes not only in a lipid-dependent manner, but also through lipid-independent pathways. The aim of our review was to shed light on the impact of PCSK9 on these factors, which are not directly related to low-density lipoprotein (LDL) cholesterol metabolism.
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spelling doaj.art-7fb6395c68db4b7daff6025df98a83fb2023-11-16T16:50:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243196610.3390/ijms24031966PCSK9 as an Atherothrombotic Risk FactorTadeja Sotler0Miran Šebeštjen1Department of Cardiology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaDepartment of Cardiology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaDisturbances in lipid metabolism are among the most important risk factors for atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein in lipid metabolism that is also involved in the production of inflammatory cytokines, endothelial dysfunction and aherosclerotic plaque development. Studies have shown a connection between PCSK9 and various indicators of inflammation. Signalling pathways that include PCSK9 play important role in the initiation and development of atherosclerotic lesions by inducing vascular inflammation. Studies so far have suggested that PCSK9 is associated with procoagulation, enhancing the development of atherosclerosis. Experimentally, it was also found that an increased concentration of PCSK9 significantly accelerated the apoptosis of endothelial cells and reduced endothelial function, which created conditions for the development of atherosclerosis. PCSK9 inhibitors can therefore improve clinical outcomes not only in a lipid-dependent manner, but also through lipid-independent pathways. The aim of our review was to shed light on the impact of PCSK9 on these factors, which are not directly related to low-density lipoprotein (LDL) cholesterol metabolism.https://www.mdpi.com/1422-0067/24/3/1966PCSK9LDL cholesterolatherosclerosisinflammationcoagulation
spellingShingle Tadeja Sotler
Miran Šebeštjen
PCSK9 as an Atherothrombotic Risk Factor
International Journal of Molecular Sciences
PCSK9
LDL cholesterol
atherosclerosis
inflammation
coagulation
title PCSK9 as an Atherothrombotic Risk Factor
title_full PCSK9 as an Atherothrombotic Risk Factor
title_fullStr PCSK9 as an Atherothrombotic Risk Factor
title_full_unstemmed PCSK9 as an Atherothrombotic Risk Factor
title_short PCSK9 as an Atherothrombotic Risk Factor
title_sort pcsk9 as an atherothrombotic risk factor
topic PCSK9
LDL cholesterol
atherosclerosis
inflammation
coagulation
url https://www.mdpi.com/1422-0067/24/3/1966
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