title: The complexity of lipoprotein (a) lowering by PCSK9 monoclonal antibodies.
abstract: Since 2012, clinical trials dedicated to proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition with monoclonal antibodies (mAbs) have unambiguously demonstrated robust reductions not only in low-density lipoprotein (LDL) cholesterol (LDL-C) but also in lipoprotein (a) [Lp(a)] levels. The scientific literature published prior to those studies did not provide any evidence for a link between PCSK9 and Lp(a) metabolism. More recent investigations, either in vitro or in vivo, have attempted to unravel the mechanism(s) by which PCSK9 mAbs reduce circulating Lp(a) levels, with some showing a specific implication of the LDL receptor (LDLR) in Lp(a) clearance whereas others found no significant role for the LDLR in that process. This elusive pathway appears clearly distinct from that of the widely prescribed statins that also enhance LDLR function but do not lower circulating Lp (a) levels in humans. So how does PCSK9 inhibition with mAbs reduce Lp(a)? This still remains to be established.
authors.affiliation: Inserm, UMR 1188 DéTROI, Sainte-Clotilde, 97490 France gilles.lambert@univ-reunion.fr.|Université de la Réunion, UMR 1188 DéTROI, Saint-Denis, 97400 France.|CHU de la Réunion, Saint-Denis, 97400 France.|Faculté de Médecine, Université de Nantes, UMR 1280 PhAN, Nantes, 44000 France.|Inra, UMR 1280 PhAN, Nantes, 44000 France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Lambert
authors.affiliation: Faculté de Médecine, Université de Nantes, UMR 1280 PhAN, Nantes, 44000 France.|Inra, UMR 1280 PhAN, Nantes, 44000 France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Thedrez
authors.affiliation: Faculté de Médecine, Université de Nantes, UMR 1280 PhAN, Nantes, 44000 France.|Inra, UMR 1280 PhAN, Nantes, 44000 France.
authors.forename: Mikaël
authors.initials: M
authors.lastname: Croyal
authors.affiliation: Inserm, UMR 1188 DéTROI, Sainte-Clotilde, 97490 France.|Université de la Réunion, UMR 1188 DéTROI, Saint-Denis, 97400 France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ramin-Mangata
authors.affiliation: Inserm, UMR 1188 DéTROI, Sainte-Clotilde, 97490 France.|Université de la Réunion, UMR 1188 DéTROI, Saint-Denis, 97400 France.|CHU de la Réunion, Saint-Denis, 97400 France.
authors.forename: David
authors.initials: D
authors.lastname: Couret
authors.affiliation: Inserm, UMR 1188 DéTROI, Sainte-Clotilde, 97490 France.|Université de la Réunion, UMR 1188 DéTROI, Saint-Denis, 97400 France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Diotel
authors.affiliation: Inserm, UMR 1188 DéTROI, Sainte-Clotilde, 97490 France.|Université de la Réunion, UMR 1188 DéTROI, Saint-Denis, 97400 France.|CHU de la Réunion, Saint-Denis, 97400 France.|Faculté de Médecine, Université de Nantes, UMR 1280 PhAN, Nantes, 44000 France.|Inra, UMR 1280 PhAN, Nantes, 44000 France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Nobécourt-Dupuy
authors.affiliation: Faculté de Médecine, Université de Nantes, UMR 1280 PhAN, Nantes, 44000 France.|Inra, UMR 1280 PhAN, Nantes, 44000 France.|Service d'Endocrinologie, CHU de Nantes, Nantes, 44000 France.
authors.forename: Michel
authors.initials: M
authors.lastname: Krempf
authors.affiliation: Sanofi R&D, Chilly-Mazarin, 91380 France.
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: LeBail
authors.affiliation: Sanofi R&D, Chilly-Mazarin, 91380 France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Poirier
authors.affiliation: Sanofi R&D, Chilly-Mazarin, 91380 France.
authors.forename: Jorg
authors.initials: J
authors.lastname: Blankenstein
authors.affiliation: Sanofi R&D, Chilly-Mazarin, 91380 France.
authors.forename: Elise F
authors.initials: EF
authors.lastname: Villard
authors.affiliation: Sanofi R&D, Chilly-Mazarin, 91380 France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Guillot
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017270:Lipoprotein(a) / Q000097:blood*; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000276:immunology; D011973:Receptors, LDL / Q000502:physiology; D012107:Research Design
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000960:Hypolipidemic Agents; D017270:Lipoprotein(a); D000091362:PCSK9 Inhibitors; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C571059:alirocumab
keywords: lipoprotein (a); low-density lipoprotein (LDL) receptor; proprotein convertase subtilisin kexin type 9 (PCSK9); statins