Insight into the Evolving Role of PCSK9
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the last discovered member of the family of proprotein convertases (PCs), mainly synthetized in hepatic cells. This serine protease plays a pivotal role in the reduction of the number of low-density lipoprotein receptors (LDLRs) on the surface...
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MDPI AG
2022-03-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/3/256 |
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| author | Mateusz Maligłówka Michał Kosowski Marcin Hachuła Marcin Cyrnek Łukasz Bułdak Marcin Basiak Aleksandra Bołdys Grzegorz Machnik Rafał Jakub Bułdak Bogusław Okopień |
| author_facet | Mateusz Maligłówka Michał Kosowski Marcin Hachuła Marcin Cyrnek Łukasz Bułdak Marcin Basiak Aleksandra Bołdys Grzegorz Machnik Rafał Jakub Bułdak Bogusław Okopień |
| author_sort | Mateusz Maligłówka |
| collection | DOAJ |
| description | Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the last discovered member of the family of proprotein convertases (PCs), mainly synthetized in hepatic cells. This serine protease plays a pivotal role in the reduction of the number of low-density lipoprotein receptors (LDLRs) on the surface of hepatocytes, which leads to an increase in the level of cholesterol in the blood. This mechanism and the fact that gain of function (GOF) mutations in <i>PCSK9</i> are responsible for causing familial hypercholesterolemia whereas loss-of-function (LOF) mutations are associated with hypocholesterolemia, prompted the invention of drugs that block PCSK9 action. The high efficiency of PCSK9 inhibitors (e.g., alirocumab, evolocumab) in decreasing cardiovascular risk, pleiotropic effects of other lipid-lowering drugs (e.g., statins) and the multifunctional character of other proprotein convertases, were the cause for proceeding studies on functions of PCSK9 beyond cholesterol metabolism. In this article, we summarize the current knowledge on the roles that PCSK9 plays in different tissues and perspectives for its clinical use. |
| first_indexed | 2024-03-09T13:20:54Z |
| format | Article |
| id | doaj.art-f3be353381554a89a259aa08885e5fae |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T13:20:54Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-f3be353381554a89a259aa08885e5fae2023-11-30T21:30:02ZengMDPI AGMetabolites2218-19892022-03-0112325610.3390/metabo12030256Insight into the Evolving Role of PCSK9Mateusz Maligłówka0Michał Kosowski1Marcin Hachuła2Marcin Cyrnek3Łukasz Bułdak4Marcin Basiak5Aleksandra Bołdys6Grzegorz Machnik7Rafał Jakub Bułdak8Bogusław Okopień9Department of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-007 Katowice, PolandDepartment of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-007 Katowice, PolandDepartment of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-007 Katowice, PolandDepartment of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-007 Katowice, PolandDepartment of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-007 Katowice, PolandDepartment of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-007 Katowice, PolandDepartment of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-007 Katowice, PolandDepartment of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-007 Katowice, PolandInstitute of Medical Sciences, University of Opole, 45-040 Opole, PolandDepartment of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-007 Katowice, PolandProprotein convertase subtilisin/kexin type 9 (PCSK9) is the last discovered member of the family of proprotein convertases (PCs), mainly synthetized in hepatic cells. This serine protease plays a pivotal role in the reduction of the number of low-density lipoprotein receptors (LDLRs) on the surface of hepatocytes, which leads to an increase in the level of cholesterol in the blood. This mechanism and the fact that gain of function (GOF) mutations in <i>PCSK9</i> are responsible for causing familial hypercholesterolemia whereas loss-of-function (LOF) mutations are associated with hypocholesterolemia, prompted the invention of drugs that block PCSK9 action. The high efficiency of PCSK9 inhibitors (e.g., alirocumab, evolocumab) in decreasing cardiovascular risk, pleiotropic effects of other lipid-lowering drugs (e.g., statins) and the multifunctional character of other proprotein convertases, were the cause for proceeding studies on functions of PCSK9 beyond cholesterol metabolism. In this article, we summarize the current knowledge on the roles that PCSK9 plays in different tissues and perspectives for its clinical use.https://www.mdpi.com/2218-1989/12/3/256PCSK9cholesterolanti-PCSK9cardiovascular diseasesgeneticatherosclerosis |
| spellingShingle | Mateusz Maligłówka Michał Kosowski Marcin Hachuła Marcin Cyrnek Łukasz Bułdak Marcin Basiak Aleksandra Bołdys Grzegorz Machnik Rafał Jakub Bułdak Bogusław Okopień Insight into the Evolving Role of PCSK9 Metabolites PCSK9 cholesterol anti-PCSK9 cardiovascular diseases genetic atherosclerosis |
| title | Insight into the Evolving Role of PCSK9 |
| title_full | Insight into the Evolving Role of PCSK9 |
| title_fullStr | Insight into the Evolving Role of PCSK9 |
| title_full_unstemmed | Insight into the Evolving Role of PCSK9 |
| title_short | Insight into the Evolving Role of PCSK9 |
| title_sort | insight into the evolving role of pcsk9 |
| topic | PCSK9 cholesterol anti-PCSK9 cardiovascular diseases genetic atherosclerosis |
| url | https://www.mdpi.com/2218-1989/12/3/256 |
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