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Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia
The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9), a serine protease which binds to the low-density lipoprotein (LDL) receptors and targets the receptors for lysosomal degradation, offered an additional route through which plasma LDL-cholesterol (LDL-C) levels can be controlled....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163360/ https://www.ncbi.nlm.nih.gov/pubmed/30011788 http://dx.doi.org/10.3390/diseases6030063 |
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author | Kosmas, Constantine E. Muñoz Estrella, Alba Sourlas, Andreas Silverio, Delia Hilario, Elizabeth Montan, Peter D. Guzman, Eliscer |
author_facet | Kosmas, Constantine E. Muñoz Estrella, Alba Sourlas, Andreas Silverio, Delia Hilario, Elizabeth Montan, Peter D. Guzman, Eliscer |
author_sort | Kosmas, Constantine E. |
collection | PubMed |
description | The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9), a serine protease which binds to the low-density lipoprotein (LDL) receptors and targets the receptors for lysosomal degradation, offered an additional route through which plasma LDL-cholesterol (LDL-C) levels can be controlled. Initially, the therapeutic approaches to reduce circulating levels of PCSK9 were focused on the use of monoclonal antibodies. To that effect, evolocumab and alirocumab, two human monoclonal antibodies directed against PCSK9, given on a background of statin therapy, have been shown to markedly decrease LDL-C levels and significantly reduce cardiovascular risk. The small interfering RNA (siRNA) molecules have been used recently to target the hepatic production of PCSK9. siRNA interferes with the expression of specific genes with complementary nucleotide sequences by affecting the degradation of mRNA post-transcription, thus preventing translation. Inclisiran is a long-acting, synthetic siRNA directed against PCSK9 and it has been shown to significantly decrease hepatic production of PCSK9 and cause a marked reduction in LDL-C levels. This review aims to present and discuss the current clinical and scientific evidence pertaining to inclisiran, which is a new promising agent in the management of hypercholesterolemia. |
format | Online Article Text |
id | pubmed-6163360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61633602018-10-11 Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia Kosmas, Constantine E. Muñoz Estrella, Alba Sourlas, Andreas Silverio, Delia Hilario, Elizabeth Montan, Peter D. Guzman, Eliscer Diseases Review The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9), a serine protease which binds to the low-density lipoprotein (LDL) receptors and targets the receptors for lysosomal degradation, offered an additional route through which plasma LDL-cholesterol (LDL-C) levels can be controlled. Initially, the therapeutic approaches to reduce circulating levels of PCSK9 were focused on the use of monoclonal antibodies. To that effect, evolocumab and alirocumab, two human monoclonal antibodies directed against PCSK9, given on a background of statin therapy, have been shown to markedly decrease LDL-C levels and significantly reduce cardiovascular risk. The small interfering RNA (siRNA) molecules have been used recently to target the hepatic production of PCSK9. siRNA interferes with the expression of specific genes with complementary nucleotide sequences by affecting the degradation of mRNA post-transcription, thus preventing translation. Inclisiran is a long-acting, synthetic siRNA directed against PCSK9 and it has been shown to significantly decrease hepatic production of PCSK9 and cause a marked reduction in LDL-C levels. This review aims to present and discuss the current clinical and scientific evidence pertaining to inclisiran, which is a new promising agent in the management of hypercholesterolemia. MDPI 2018-07-13 /pmc/articles/PMC6163360/ /pubmed/30011788 http://dx.doi.org/10.3390/diseases6030063 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Kosmas, Constantine E. Muñoz Estrella, Alba Sourlas, Andreas Silverio, Delia Hilario, Elizabeth Montan, Peter D. Guzman, Eliscer Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia |
title | Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia |
title_full | Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia |
title_fullStr | Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia |
title_full_unstemmed | Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia |
title_short | Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia |
title_sort | inclisiran: a new promising agent in the management of hypercholesterolemia |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163360/ https://www.ncbi.nlm.nih.gov/pubmed/30011788 http://dx.doi.org/10.3390/diseases6030063 |
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