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Lipoprotein(a) Cellular Uptake Ex Vivo and Hepatic Capture In Vivo Is Insensitive to PCSK9 Inhibition With Alirocumab
Lipoprotein(a) (Lp[a]) is the most common genetically inherited risk factor for cardiovascular disease. Many aspects of Lp(a) metabolism remain unknown. We assessed the uptake of fluorescent Lp(a) in primary human lymphocytes as well as Lp(a) hepatic capture in a mouse model in which endogenous hepa...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315184/ https://www.ncbi.nlm.nih.gov/pubmed/32613143 http://dx.doi.org/10.1016/j.jacbts.2020.03.008 |
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author | Chemello, Kévin Beeské, Sandra Trang Tran, Thi Thu Blanchard, Valentin Villard, Elise F. Poirier, Bruno Le Bail, Jean-Christophe Dargazanli, Gihad Ho-Van-Guimbal, Sophie Boulay, Denis Bergis, Olivier Pruniaux, Marie-Pierre Croyal, Mikaël Janiak, Philip Guillot, Etienne Lambert, Gilles |
author_facet | Chemello, Kévin Beeské, Sandra Trang Tran, Thi Thu Blanchard, Valentin Villard, Elise F. Poirier, Bruno Le Bail, Jean-Christophe Dargazanli, Gihad Ho-Van-Guimbal, Sophie Boulay, Denis Bergis, Olivier Pruniaux, Marie-Pierre Croyal, Mikaël Janiak, Philip Guillot, Etienne Lambert, Gilles |
author_sort | Chemello, Kévin |
collection | PubMed |
description | Lipoprotein(a) (Lp[a]) is the most common genetically inherited risk factor for cardiovascular disease. Many aspects of Lp(a) metabolism remain unknown. We assessed the uptake of fluorescent Lp(a) in primary human lymphocytes as well as Lp(a) hepatic capture in a mouse model in which endogenous hepatocytes have been ablated and replaced with human ones. Modulation of LDLR expression with the PCSK9 inhibitor alirocumab did not alter the cellular or the hepatic uptake of Lp(a), demonstrating that the LDL receptor is not a major route for Lp(a) plasma clearance. These results have clinical implications because they underpin why statins are not efficient at reducing Lp(a). |
format | Online Article Text |
id | pubmed-7315184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-73151842020-06-30 Lipoprotein(a) Cellular Uptake Ex Vivo and Hepatic Capture In Vivo Is Insensitive to PCSK9 Inhibition With Alirocumab Chemello, Kévin Beeské, Sandra Trang Tran, Thi Thu Blanchard, Valentin Villard, Elise F. Poirier, Bruno Le Bail, Jean-Christophe Dargazanli, Gihad Ho-Van-Guimbal, Sophie Boulay, Denis Bergis, Olivier Pruniaux, Marie-Pierre Croyal, Mikaël Janiak, Philip Guillot, Etienne Lambert, Gilles JACC Basic Transl Sci PRECLINICAL RESEARCH Lipoprotein(a) (Lp[a]) is the most common genetically inherited risk factor for cardiovascular disease. Many aspects of Lp(a) metabolism remain unknown. We assessed the uptake of fluorescent Lp(a) in primary human lymphocytes as well as Lp(a) hepatic capture in a mouse model in which endogenous hepatocytes have been ablated and replaced with human ones. Modulation of LDLR expression with the PCSK9 inhibitor alirocumab did not alter the cellular or the hepatic uptake of Lp(a), demonstrating that the LDL receptor is not a major route for Lp(a) plasma clearance. These results have clinical implications because they underpin why statins are not efficient at reducing Lp(a). Elsevier 2020-05-06 /pmc/articles/PMC7315184/ /pubmed/32613143 http://dx.doi.org/10.1016/j.jacbts.2020.03.008 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | PRECLINICAL RESEARCH Chemello, Kévin Beeské, Sandra Trang Tran, Thi Thu Blanchard, Valentin Villard, Elise F. Poirier, Bruno Le Bail, Jean-Christophe Dargazanli, Gihad Ho-Van-Guimbal, Sophie Boulay, Denis Bergis, Olivier Pruniaux, Marie-Pierre Croyal, Mikaël Janiak, Philip Guillot, Etienne Lambert, Gilles Lipoprotein(a) Cellular Uptake Ex Vivo and Hepatic Capture In Vivo Is Insensitive to PCSK9 Inhibition With Alirocumab |
title | Lipoprotein(a) Cellular Uptake Ex Vivo and Hepatic Capture In Vivo Is Insensitive to PCSK9 Inhibition With Alirocumab |
title_full | Lipoprotein(a) Cellular Uptake Ex Vivo and Hepatic Capture In Vivo Is Insensitive to PCSK9 Inhibition With Alirocumab |
title_fullStr | Lipoprotein(a) Cellular Uptake Ex Vivo and Hepatic Capture In Vivo Is Insensitive to PCSK9 Inhibition With Alirocumab |
title_full_unstemmed | Lipoprotein(a) Cellular Uptake Ex Vivo and Hepatic Capture In Vivo Is Insensitive to PCSK9 Inhibition With Alirocumab |
title_short | Lipoprotein(a) Cellular Uptake Ex Vivo and Hepatic Capture In Vivo Is Insensitive to PCSK9 Inhibition With Alirocumab |
title_sort | lipoprotein(a) cellular uptake ex vivo and hepatic capture in vivo is insensitive to pcsk9 inhibition with alirocumab |
topic | PRECLINICAL RESEARCH |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315184/ https://www.ncbi.nlm.nih.gov/pubmed/32613143 http://dx.doi.org/10.1016/j.jacbts.2020.03.008 |
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