PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia

We investigated the potential of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies torestore macrophage cholesterol efflux in subjects with heterozygous familial hypercholesterolemia (FH)and to enhance the macrophage-specific reverse cholesterol transport pathway in mice. Analyses ofmac...

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Bibliographic Details
Authors: Borràs, Carla|||0000-0002-0998-7855, Canyelles, Marina|||0000-0002-0278-5337, Girona, Josefa, Ibarretxe, Daiana, Santos, David|||0000-0003-1157-4969, Revilla, Giovanna|||0000-0003-2971-5651, Llorente-Cortés, Vicenta|||0000-0002-0067-7201, Rotllan, Noemi|||0000-0002-0587-8045, Kovanen, Petri T., Jauhiainen, Matti|||0000-0002-3836-3785, Lee-Rueckert, Miriam, Masana, Luis|||0000-0002-0789-4954, Arrieta, Francisco|||0000-0001-7571-0451, Martínez-Botas, Javier|||0000-0002-5190-3619, Gómez-Coronado, Diego|||0000-0002-8382-3920, Ribalta, Josep|||0000-0002-8879-4719, Tondo Colomer, Mireia|||0000-0002-0301-9984, Blanco Vaca, Francisco|||0000-0001-7380-5385, Escolà-Gil, Joan Carles|||0000-0001-9021-2485
Format: article
Publication Date:2024
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:319949
Online Access:https://ddd.uab.cat/record/319949
https://dx.doi.org/urn:doi:10.1016/j.jacbts.2024.06.008
Access Level:Open access
Keyword:Cholesterol
Familial hypercholesterolemia
HDL
LDL
Macrophages
Mice
PCSK9
Reverse cholesterol transport
Description
Summary:We investigated the potential of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies torestore macrophage cholesterol efflux in subjects with heterozygous familial hypercholesterolemia (FH)and to enhance the macrophage-specific reverse cholesterol transport pathway in mice. Analyses ofmacrophage-derived cholesterol distribution of plasma from FH patients revealed that low-density li-poprotein (LDL) particles contained less, and high-density lipoprotein particles contained more radio-labeled cholesterol after treatment with either PCSK9 inhibitor. PCSK9 antibodies facilitated thetransfer of macrophage-derived cholesterol and LDL-derived cholesterol to feces exclusively inheterozygous LDL receptor-deficient mice expressing human APOB100. PCSK9 inhibitors act aspositive regulators of the macrophage-specific reverse cholesterol transport pathway in individuals withheterozygous FH.

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