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

Identifier:  imarina:9387511

Handle: https://hdl.handle.net/20.500.11797/imarina9387511

Authors:  Borràs C; Canyelles M; Girona J; Ibarretxe D; Santos D; Revilla G; Llorente-Cortes V; Rotllan N; Kovanen PT; Jauhiainen M; Lee-Rueckert M; Masana L; Arrieta F; Martínez-Botas J; Gómez-Coronado D; Ribalta J; Tondo M; Blanco-Vaca F; Escolà-Gil JC

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.