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

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

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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Autores:	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
Tipo de recurso:	artículo
Fecha de publicación:	2024
País:	España
Institución:	Universitat Autònoma de Barcelona
Repositorio:	Dipòsit Digital de Documents de la UAB
Idioma:	inglés
OAI Identifier:	oai:ddd.uab.cat:319949
Acceso en línea:	https://ddd.uab.cat/record/319949 https://dx.doi.org/urn:doi:10.1016/j.jacbts.2024.06.008
Access Level:	acceso abierto
Palabra clave:	Cholesterol Familial hypercholesterolemia HDL LDL Macrophages Mice PCSK9 Reverse cholesterol transport

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repository_id_str
spelling	PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial HypercholesterolemiaBorràs, Carla\|\|\|0000-0002-0998-7855Canyelles, Marina\|\|\|0000-0002-0278-5337Girona, JosefaIbarretxe, DaianaSantos, David\|\|\|0000-0003-1157-4969Revilla, Giovanna\|\|\|0000-0003-2971-5651Llorente-Cortés, Vicenta\|\|\|0000-0002-0067-7201Rotllan, Noemi\|\|\|0000-0002-0587-8045Kovanen, Petri T.Jauhiainen, Matti\|\|\|0000-0002-3836-3785Lee-Rueckert, MiriamMasana, Luis\|\|\|0000-0002-0789-4954Arrieta, Francisco\|\|\|0000-0001-7571-0451Martínez-Botas, Javier\|\|\|0000-0002-5190-3619Gómez-Coronado, Diego\|\|\|0000-0002-8382-3920Ribalta, Josep\|\|\|0000-0002-8879-4719Tondo Colomer, Mireia\|\|\|0000-0002-0301-9984Blanco Vaca, Francisco\|\|\|0000-0001-7380-5385Escolà-Gil, Joan Carles\|\|\|0000-0001-9021-2485CholesterolFamilial hypercholesterolemiaHDLLDLMacrophagesMicePCSK9Reverse cholesterol transportWe 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. 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/319949https://dx.doi.org/urn:doi:10.1016/j.jacbts.2024.06.008reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI2100140Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI2101523Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI2300232Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 JR22/00003Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-098113-B-I00Fundació la Marató de TV3 https://doi.org/10.13039/100008666 12/C/2015Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RYC-201722879Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 FPU20/07440open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3199492026-06-06T12:50:31Z
dc.title.none.fl_str_mv	PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia
title	PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia
spellingShingle	PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia Borràs, Carla\|\|\|0000-0002-0998-7855 Cholesterol Familial hypercholesterolemia HDL LDL Macrophages Mice PCSK9 Reverse cholesterol transport
title_short	PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia
title_full	PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia
title_fullStr	PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia
title_full_unstemmed	PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia
title_sort	PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia
dc.creator.none.fl_str_mv	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
author	Borràs, Carla\|\|\|0000-0002-0998-7855
author_facet	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
author_role	author
author2	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
author2_role	author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Cholesterol Familial hypercholesterolemia HDL LDL Macrophages Mice PCSK9 Reverse cholesterol transport
topic	Cholesterol Familial hypercholesterolemia HDL LDL Macrophages Mice PCSK9 Reverse cholesterol transport
description	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.
publishDate	2024
dc.date.none.fl_str_mv	2 2024-01-01 2024 2024-01-01
dc.type.none.fl_str_mv	Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://ddd.uab.cat/record/319949 https://dx.doi.org/urn:doi:10.1016/j.jacbts.2024.06.008
url	https://ddd.uab.cat/record/319949 https://dx.doi.org/urn:doi:10.1016/j.jacbts.2024.06.008
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI2100140 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI2101523 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI2300232 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 JR22/00003 Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-098113-B-I00 Fundació la Marató de TV3 https://doi.org/10.13039/100008666 12/C/2015 Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RYC-201722879 Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 FPU20/07440
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.source.none.fl_str_mv	reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona
instname_str	Universitat Autònoma de Barcelona
reponame_str	Dipòsit Digital de Documents de la UAB
collection	Dipòsit Digital de Documents de la UAB
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PCSK9 Antibodies Treatment Specifically Enhances the Macrophage-specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia

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