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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
PRECLINICAL RESEARCH
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
Descripción
Sumario: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).

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