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

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

  • JACC Basic Transl Sci. 2016 Oct;1(6):419-427. doi: 10.1016/j.jacbts.2016.06.006.
Elise F Villard 1,  Aurélie Thedrez 2 3,  Jorg Blankenstein 1,  Mikaël Croyal 2,  Thi-Thu-Trang Tran 1,  Bruno Poirier 1,  Jean-Christophe Le Bail 1,  Stéphane Illiano 1,  Estelle Nobécourt 2 3,  Michel Krempf 2 3,  Dirk J Blom 4,  A David Marais 5,  Philip Janiak 1,  Anthony J Muslin 1,  Etienne Guillot 1,  Gilles Lambert 2 6 7 8
Affiliations

Affiliations

  • 1 Sanofi Recherche Développement, Chilly-Mazarin, France.
  • 2 Inra UMR 1280, Nantes, France.
  • 3 Université de Nantes UMR1280, Faculté de Médecine, Nantes, France.
  • 4 Division of Lipidology, Department of Internal Medicine, University of Cape Town, Cape Town, South Africa.
  • 5 Division of Chemical Pathology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
  • 6 Inserm UMR 1188, Sainte-Clotilde, France.
  • 7 Université de la Réunion UMR1188, Faculté de Médecine, Saint-Denis, France.
  • 8 CHU de la Réunion, Saint Denis, France.
PMID: 29308438 DOI: 10.1016/j.jacbts.2016.06.006
Abstract

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.

Keywords

LDL receptor; PCSK9; familial hypercholesterolemia; lipoprotein(a); primary human hepatocytes.

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