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 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 o...

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Detalhes bibliográficos
Autores: Borràs, Carla, Canyelles, Marina, Girona, Josefa, Ibarretxe, Daiana, Santos, David, Revilla, Giovanna, Llorente-Cortés, Vicenta, Rotllan, Noemí, Kovanen, Petri T., Jauhiainen, Matti, Lee-Rueckert, Miriam, Masana, Luis, Arrieta, Francisco, Martínez-Botas, Javier, Gómez-Coronado, Diego, Ribalta, Josep, Tondo, Mireia, Blanco-Vaca, Francisco, Escolà-Gil, Joan Carles
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2024
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/374270
Acesso em linha:http://hdl.handle.net/10261/374270
https://api.elsevier.com/content/abstract/scopus_id/85203840652
Access Level:Acceso aberto
Palavra-chave:HDL
LDL
PCSK9
Cholesterol
Familial hypercholesterolemia
Macrophages
Mice
Reverse cholesterol transport
Descrição
Resumo: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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