Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice

Clinical complications associated with atherosclerotic plaques arise from luminal obstruction due to plaque growth or destabilization leading to rupture. Tumour necrosis factor ligand superfamily member 12 (TNFSF12) also known as TNF-related weak inducer of apoptosis (TWEAK) is a proinflammatory cyt...

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Detalles Bibliográficos
Autores: Sastre, Cristina, Fernández‐Laso, Valvanera, Madrigal‐Matute, Julio, Muñoz‐García, Begoña, Moreno, Juan, Pastor Vargas, Carlos, Llamas‐Granda, Patricia, Burkly, Linda, Egido, Jesús, Martín‐Ventura, José, Blanco‐Colio, Luis
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/107322
Acceso en línea:https://hdl.handle.net/20.500.14352/107322
Access Level:acceso abierto
Palabra clave:611.1
616.13-002.2
TWEAK
Atherosclerosis
Inflammation
Plaque stability
Medicina
Sistema cardiovascular
32 Ciencias Médicas
3207 Patología
3207.02 Arteriosclerosis
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oai_identifier_str oai:docta.ucm.es:20.500.14352/107322
network_acronym_str ES
network_name_str España
repository_id_str
spelling Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in miceSastre, CristinaFernández‐Laso, ValvaneraMadrigal‐Matute, JulioMuñoz‐García, BegoñaMoreno, JuanPastor Vargas, CarlosLlamas‐Granda, PatriciaBurkly, LindaEgido, JesúsMartín‐Ventura, JoséBlanco‐Colio, Luis611.1616.13-002.2TWEAKAtherosclerosisInflammationPlaque stabilityMedicinaSistema cardiovascular32 Ciencias Médicas3207 Patología3207.02 ArteriosclerosisClinical complications associated with atherosclerotic plaques arise from luminal obstruction due to plaque growth or destabilization leading to rupture. Tumour necrosis factor ligand superfamily member 12 (TNFSF12) also known as TNF-related weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine that participates in atherosclerotic plaque development, but its role in plaque stability remains unclear. Using two different approaches, genetic deletion of TNFSF12 and treatment with a TWEAK blocking mAb in atherosclerosis-prone mice, we have analysed the effect of TWEAK inhibition on atherosclerotic plaques progression and stability. Mice lacking both TNFSF12 and Apolipoprotein E (TNFSF12(-/-) ApoE(-/-) ) exhibited a diminished atherosclerotic burden and lesion size in their aorta. Advanced atherosclerotic plaques of TNFSF12(-/-) ApoE(-/-) or anti-TWEAK treated mice exhibited an increase collagen/lipid and vascular smooth muscle cell/macrophage ratios compared with TNFSF12(+/+) ApoE(-/-) control mice, reflecting a more stable plaque phenotype. These changes are related with two different mechanisms, reduction of the inflammatory response (chemokines expression and secretion and nuclear factor kappa B activation) and decrease of metalloproteinase activity in atherosclerotic plaques of TNFSF12(-/-) ApoE(-/-) . A similar phenotype was observed with anti-TWEAK mAb treatment in TNFSF12(+/+) ApoE(-/-) mice. Brachiocephalic arteries were also examined since they exhibit additional features akin to human atherosclerotic plaques associated with instability and rupture. Features of greater plaque stability including augmented collagen/lipid ratio, reduced macrophage content, and less presence of lateral xanthomas, buried caps, medial erosion, intraplaque haemorrhage and calcium content were present in TNFSF12(-/-) ApoE(-/-) or anti-TWEAK treatment in TNFSF12(+/+) ApoE(-/-) mice. Overall, our data indicate that anti-TWEAK treatment has the capacity to diminish proinflamatory response associated with atherosclerotic plaque progression and to alter plaque morphology towards a stable phenotype.WileyUniversidad Complutense de Madrid20142014-01-0120142014-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/107322reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1073222026-06-02T12:44:21Z
dc.title.none.fl_str_mv Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice
title Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice
spellingShingle Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice
Sastre, Cristina
611.1
616.13-002.2
TWEAK
Atherosclerosis
Inflammation
Plaque stability
Medicina
Sistema cardiovascular
32 Ciencias Médicas
3207 Patología
3207.02 Arteriosclerosis
title_short Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice
title_full Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice
title_fullStr Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice
title_full_unstemmed Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice
title_sort Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice
dc.creator.none.fl_str_mv Sastre, Cristina
Fernández‐Laso, Valvanera
Madrigal‐Matute, Julio
Muñoz‐García, Begoña
Moreno, Juan
Pastor Vargas, Carlos
Llamas‐Granda, Patricia
Burkly, Linda
Egido, Jesús
Martín‐Ventura, José
Blanco‐Colio, Luis
author Sastre, Cristina
author_facet Sastre, Cristina
Fernández‐Laso, Valvanera
Madrigal‐Matute, Julio
Muñoz‐García, Begoña
Moreno, Juan
Pastor Vargas, Carlos
Llamas‐Granda, Patricia
Burkly, Linda
Egido, Jesús
Martín‐Ventura, José
Blanco‐Colio, Luis
author_role author
author2 Fernández‐Laso, Valvanera
Madrigal‐Matute, Julio
Muñoz‐García, Begoña
Moreno, Juan
Pastor Vargas, Carlos
Llamas‐Granda, Patricia
Burkly, Linda
Egido, Jesús
Martín‐Ventura, José
Blanco‐Colio, Luis
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 611.1
616.13-002.2
TWEAK
Atherosclerosis
Inflammation
Plaque stability
Medicina
Sistema cardiovascular
32 Ciencias Médicas
3207 Patología
3207.02 Arteriosclerosis
topic 611.1
616.13-002.2
TWEAK
Atherosclerosis
Inflammation
Plaque stability
Medicina
Sistema cardiovascular
32 Ciencias Médicas
3207 Patología
3207.02 Arteriosclerosis
description Clinical complications associated with atherosclerotic plaques arise from luminal obstruction due to plaque growth or destabilization leading to rupture. Tumour necrosis factor ligand superfamily member 12 (TNFSF12) also known as TNF-related weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine that participates in atherosclerotic plaque development, but its role in plaque stability remains unclear. Using two different approaches, genetic deletion of TNFSF12 and treatment with a TWEAK blocking mAb in atherosclerosis-prone mice, we have analysed the effect of TWEAK inhibition on atherosclerotic plaques progression and stability. Mice lacking both TNFSF12 and Apolipoprotein E (TNFSF12(-/-) ApoE(-/-) ) exhibited a diminished atherosclerotic burden and lesion size in their aorta. Advanced atherosclerotic plaques of TNFSF12(-/-) ApoE(-/-) or anti-TWEAK treated mice exhibited an increase collagen/lipid and vascular smooth muscle cell/macrophage ratios compared with TNFSF12(+/+) ApoE(-/-) control mice, reflecting a more stable plaque phenotype. These changes are related with two different mechanisms, reduction of the inflammatory response (chemokines expression and secretion and nuclear factor kappa B activation) and decrease of metalloproteinase activity in atherosclerotic plaques of TNFSF12(-/-) ApoE(-/-) . A similar phenotype was observed with anti-TWEAK mAb treatment in TNFSF12(+/+) ApoE(-/-) mice. Brachiocephalic arteries were also examined since they exhibit additional features akin to human atherosclerotic plaques associated with instability and rupture. Features of greater plaque stability including augmented collagen/lipid ratio, reduced macrophage content, and less presence of lateral xanthomas, buried caps, medial erosion, intraplaque haemorrhage and calcium content were present in TNFSF12(-/-) ApoE(-/-) or anti-TWEAK treatment in TNFSF12(+/+) ApoE(-/-) mice. Overall, our data indicate that anti-TWEAK treatment has the capacity to diminish proinflamatory response associated with atherosclerotic plaque progression and to alter plaque morphology towards a stable phenotype.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-01-01
2014
2014-01-01
dc.type.none.fl_str_mv journal 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://hdl.handle.net/20.500.14352/107322
url https://hdl.handle.net/20.500.14352/107322
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://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
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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