C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression

Background: Formation of haemorrhagic neovessels in the intima of developing atherosclerotic plaques is thought to significantly contribute to plaque instability resulting in thrombosis. C-reactive protein (CRP) is an acute phase reactant whose expression in the vascular wall, in particular, in reac...

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Autores: Turu, Marta M., Slevin, Mark, Matou, Sabine, West, David, Rodríguez, Cristina, Luque Gómez, Ana, Grau Olivares, Marta, Badimón, Lina, 1953-, Martínez González, José, Krupinski, Jerzy
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2008
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/126420
Acceso en línea:https://hdl.handle.net/2445/126420
Access Level:acceso abierto
Palabra clave:Trombosi
Angiogènesi
Thrombosis
Neovascularization
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spelling C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expressionTuru, Marta M.Slevin, MarkMatou, SabineWest, DavidRodríguez, CristinaLuque Gómez, AnaGrau Olivares, MartaBadimón, Lina, 1953-Martínez González, JoséKrupinski, JerzyTrombosiAngiogènesiThrombosisNeovascularizationBackground: Formation of haemorrhagic neovessels in the intima of developing atherosclerotic plaques is thought to significantly contribute to plaque instability resulting in thrombosis. C-reactive protein (CRP) is an acute phase reactant whose expression in the vascular wall, in particular, in reactive plaque regions, and circulating levels increase in patients at high risk of cardiovascular events. Although CRP is known to induce a pro-inflammatory phenotype in endothelial cells (EC) a direct role on modulation of angiogenesis has not been established. Results: Here, we show that CRP is a powerful inducer of angiogenesis in bovine aortic EC (BAEC) and human coronary artery EC (HCAEC). CRP, at concentrations corresponding to moderate/high risk (1-5 mu g/ml), induced a significant increase in proliferation, migration and tube-like structure formation in vitro and stimulated blood vessel formation in the chick chorioallantoic membrane assay (CAM). CRP treated with detoxi-gel columns retained such effects. Western blotting showed that CRP increased activation of early response kinase-1/2 (ERK1/2), a key protein involved in EC mitogenesis. Furthermore, using TaqMan Low-density Arrays we identified key pro-angiogenic genes induced by CRP among them were vascular endothelial cell growth factor receptor-2 (VEGFR2/KDR), platelet-derived growth factor (PDGF-BB), notch family transcription factors (Notch1 and Notch3), cysteine-rich angiogenic inducer 61 (CYR61/CCN1) and inhibitor of DNA binding/differentiation-1 (ID1). Conclusion: This data suggests a role for CRP in direct stimulation of angiogenesis and therefore may be a mediator of neovessel formation in the intima of vulnerable plaques.Biomed Central2008info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/126420Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/1471-2121-9-47BMC Cell Biology, 2008, vol. 9, num. 47https://doi.org/10.1186/1471-2121-9-47cc by (c) Turu et al., 2008http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1264202026-05-27T06:46:51Z
dc.title.none.fl_str_mv C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression
title C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression
spellingShingle C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression
Turu, Marta M.
Trombosi
Angiogènesi
Thrombosis
Neovascularization
title_short C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression
title_full C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression
title_fullStr C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression
title_full_unstemmed C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression
title_sort C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression
dc.creator.none.fl_str_mv Turu, Marta M.
Slevin, Mark
Matou, Sabine
West, David
Rodríguez, Cristina
Luque Gómez, Ana
Grau Olivares, Marta
Badimón, Lina, 1953-
Martínez González, José
Krupinski, Jerzy
author Turu, Marta M.
author_facet Turu, Marta M.
Slevin, Mark
Matou, Sabine
West, David
Rodríguez, Cristina
Luque Gómez, Ana
Grau Olivares, Marta
Badimón, Lina, 1953-
Martínez González, José
Krupinski, Jerzy
author_role author
author2 Slevin, Mark
Matou, Sabine
West, David
Rodríguez, Cristina
Luque Gómez, Ana
Grau Olivares, Marta
Badimón, Lina, 1953-
Martínez González, José
Krupinski, Jerzy
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Trombosi
Angiogènesi
Thrombosis
Neovascularization
topic Trombosi
Angiogènesi
Thrombosis
Neovascularization
description Background: Formation of haemorrhagic neovessels in the intima of developing atherosclerotic plaques is thought to significantly contribute to plaque instability resulting in thrombosis. C-reactive protein (CRP) is an acute phase reactant whose expression in the vascular wall, in particular, in reactive plaque regions, and circulating levels increase in patients at high risk of cardiovascular events. Although CRP is known to induce a pro-inflammatory phenotype in endothelial cells (EC) a direct role on modulation of angiogenesis has not been established. Results: Here, we show that CRP is a powerful inducer of angiogenesis in bovine aortic EC (BAEC) and human coronary artery EC (HCAEC). CRP, at concentrations corresponding to moderate/high risk (1-5 mu g/ml), induced a significant increase in proliferation, migration and tube-like structure formation in vitro and stimulated blood vessel formation in the chick chorioallantoic membrane assay (CAM). CRP treated with detoxi-gel columns retained such effects. Western blotting showed that CRP increased activation of early response kinase-1/2 (ERK1/2), a key protein involved in EC mitogenesis. Furthermore, using TaqMan Low-density Arrays we identified key pro-angiogenic genes induced by CRP among them were vascular endothelial cell growth factor receptor-2 (VEGFR2/KDR), platelet-derived growth factor (PDGF-BB), notch family transcription factors (Notch1 and Notch3), cysteine-rich angiogenic inducer 61 (CYR61/CCN1) and inhibitor of DNA binding/differentiation-1 (ID1). Conclusion: This data suggests a role for CRP in direct stimulation of angiogenesis and therefore may be a mediator of neovessel formation in the intima of vulnerable plaques.
publishDate 2008
dc.date.none.fl_str_mv 2008
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/126420
url https://hdl.handle.net/2445/126420
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/1471-2121-9-47
BMC Cell Biology, 2008, vol. 9, num. 47
https://doi.org/10.1186/1471-2121-9-47
dc.rights.none.fl_str_mv cc by (c) Turu et al., 2008
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Turu et al., 2008
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Biomed Central
publisher.none.fl_str_mv Biomed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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