PCSK9 Modulates the Secretion But Not the Cellular Uptake of Lipoprotein(a) Ex Vivo: An Effect Blunted by Alirocumab

To elucidate how the proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor alirocumab modulates lipoprotein(a) [Lp(a)] plasma levels, the authors performed a series of Lp(a) uptake studies in primary human hepatocytes and dermal fibroblasts and measured Lp(a) secretion from human hepatocyt...

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Published in:JACC. Basic to translational science 2016-10, Vol.1 (6), p.419-427
Main Authors: Villard, Elise F, Thedrez, Aurélie, Blankenstein, Jorg, Croyal, Mikaël, Tran, Thi-Thu-Trang, Poirier, Bruno, Le Bail, Jean-Christophe, Illiano, Stéphane, Nobécourt, Estelle, Krempf, Michel, Blom, Dirk J, Marais, A David, Janiak, Philip, Muslin, Anthony J, Guillot, Etienne, Lambert, Gilles
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Food and Nutrition
Life Sciences
PRECLINICAL RESEARCH
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container_end_page 427
container_issue 6
container_start_page 419
container_title JACC. Basic to translational science
container_volume 1
creator Villard, Elise F
Thedrez, Aurélie
Blankenstein, Jorg
Croyal, Mikaël
Tran, Thi-Thu-Trang
Poirier, Bruno
Le Bail, Jean-Christophe
Illiano, Stéphane
Nobécourt, Estelle
Krempf, Michel
Blom, Dirk J
Marais, A David
Janiak, Philip
Muslin, Anthony J
Guillot, Etienne
Lambert, Gilles
description To elucidate how the proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor alirocumab modulates lipoprotein(a) [Lp(a)] plasma levels, the authors performed a series of Lp(a) uptake studies in primary human hepatocytes and dermal fibroblasts and measured Lp(a) secretion from human hepatocytes. They found that Lp(a) cellular uptake occurred in a low-density lipoprotein receptor-independent manner. Neither PCSK9 nor alirocumab altered Lp(a) internalization. By contrast, the secretion of apolipoprotein (a) from human hepatocytes was sharply increased by PCSK9, an effect that was reversed by alirocumab. They propose that PCSK9 does not significantly modulate Lp(a) catabolism, but rather enhances the secretion of Lp(a) from liver cells.
doi_str_mv 10.1016/j.jacbts.2016.06.006
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subjects Food and Nutrition
Life Sciences
PRECLINICAL RESEARCH
title PCSK9 Modulates the Secretion But Not the Cellular Uptake of Lipoprotein(a) Ex Vivo: An Effect Blunted by Alirocumab
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