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

Overview

Journal JACC Basic Transl Sci

Date 2024 Nov 13

PMID 39534644

Authors

Carla Borras

Marina Canyelles

Josefa Girona

Daiana Ibarretxe

David Santos

Giovanna Revilla

Vicenta Llorente-Cortes

Noemi Rotllan

Petri T Kovanen

Matti Jauhiainen

Miriam Lee-Rueckert

Luis Masana

Francisco Arrieta

Javier Martinez-Botas

Diego Gomez-Coronado

Josep Ribalta

Mireia Tondo

Francisco Blanco-Vaca

Joan Carles Escola-Gil

Affiliations

Soon will be listed here.

Abstract

We investigated the potential of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies to restore macrophage cholesterol efflux in subjects with heterozygous familial hypercholesterolemia (FH) and to enhance the macrophage-specific reverse cholesterol transport pathway in mice. Analyses of macrophage-derived cholesterol distribution of plasma from FH patients revealed that low-density lipoprotein (LDL) particles contained less, and high-density lipoprotein particles contained more radiolabeled cholesterol after treatment with either PCSK9 inhibitor. PCSK9 antibodies facilitated the transfer of macrophage-derived cholesterol and LDL-derived cholesterol to feces exclusively in heterozygous LDL receptor-deficient mice expressing human APOB100. PCSK9 inhibitors act as positive regulators of the macrophage-specific reverse cholesterol transport pathway in individuals with heterozygous FH.

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