Cerebral ischaemia and matrix metalloproteinase-9 modulate the angiogenic function of early and late outgrowth endothelial progenitor cells

The enhancement of endogenous angiogenesis after stroke will be critical in neurorepair therapies where endothelial progenitor cells (EPCs) might be key players. Our aim was to determine the influence of cerebral ischaemia and the role of matrix metalloproteinase-9 (MMP-9) on the angiogenic function...

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Autores: Morancho, Anna|||0000-0001-9059-3206, Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091, Boada, Cristina, Barceló, Verónica, Giralt, Dolors, Ortega, Laura, Montaner, Joan|||0000-0003-4845-2279, Rosell Novel, Anna|||0000-0003-1082-3599
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:184942
Acceso en línea:https://ddd.uab.cat/record/184942
https://dx.doi.org/urn:doi:10.1111/jcmm.12116
Access Level:acceso abierto
Palabra clave:Endothelial progenitor cell
Matrix metalloproteinase-9
Cerebral ischaemia
Angiogenesis
Neurorepair
Stroke
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spelling Cerebral ischaemia and matrix metalloproteinase-9 modulate the angiogenic function of early and late outgrowth endothelial progenitor cellsMorancho, Anna|||0000-0001-9059-3206Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091Boada, CristinaBarceló, VerónicaGiralt, DolorsOrtega, LauraMontaner, Joan|||0000-0003-4845-2279Rosell Novel, Anna|||0000-0003-1082-3599Endothelial progenitor cellMatrix metalloproteinase-9Cerebral ischaemiaAngiogenesisNeurorepairStrokeThe enhancement of endogenous angiogenesis after stroke will be critical in neurorepair therapies where endothelial progenitor cells (EPCs) might be key players. Our aim was to determine the influence of cerebral ischaemia and the role of matrix metalloproteinase-9 (MMP-9) on the angiogenic function of EPCs. Permanent focal cerebral ischaemia was induced by middle cerebral artery (MCA) occlusion in MMP-9/knockout (MMP-9/KO) and wild-type (WT) mice. EPCs were obtained for cell counting after ischaemia (6 and 24 hrs) and in control animals. Matrigel™ assays and time-lapse imaging were conducted to monitor angiogenic function of WT and MMP9-deficient EPCs or after treatment with MMP-9 inhibitors. Focal cerebral ischaemia increased the number of early EPCs, while MMP-9 deficiency decreased their number in non-ischaemic mice and delayed their release after ischaemia. Late outgrowth endothelial cells (OECs) from ischaemic mice shaped more vessel structures than controls, while MMP-9 deficiency reduced the angiogenic abilities of OECs to form vascular networks, in vitro. Treatment with the MMP inhibitor GM6001 and the specific MMP-9 inhibitor I also decreased the number of vessel structures shaped by both human and mouse WT OECs, while exogenous MMP-9 could not revert the impaired angiogenic function in MMP-9/KO OECs. Finally, time-lapse imaging showed that the extension of vascular networks was influenced by cerebral ischaemia and MMP-9 deficiency early during the vascular network formation followed by a dynamic vessel remodelling. We conclude that focal cerebral ischaemia triggers the angiogenic responses of EPCs, while MMP-9 plays a key role in the formation of vascular networks by EPCs.Universitat Autònoma de Barcelona 22013-01-0120132013-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/184942https://dx.doi.org/urn:doi:10.1111/jcmm.12116reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI10/00694Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 ERANET-NEURON/2011-1352open 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, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1849422026-06-06T12:50:31Z
dc.title.none.fl_str_mv Cerebral ischaemia and matrix metalloproteinase-9 modulate the angiogenic function of early and late outgrowth endothelial progenitor cells
title Cerebral ischaemia and matrix metalloproteinase-9 modulate the angiogenic function of early and late outgrowth endothelial progenitor cells
spellingShingle Cerebral ischaemia and matrix metalloproteinase-9 modulate the angiogenic function of early and late outgrowth endothelial progenitor cells
Morancho, Anna|||0000-0001-9059-3206
Endothelial progenitor cell
Matrix metalloproteinase-9
Cerebral ischaemia
Angiogenesis
Neurorepair
Stroke
title_short Cerebral ischaemia and matrix metalloproteinase-9 modulate the angiogenic function of early and late outgrowth endothelial progenitor cells
title_full Cerebral ischaemia and matrix metalloproteinase-9 modulate the angiogenic function of early and late outgrowth endothelial progenitor cells
title_fullStr Cerebral ischaemia and matrix metalloproteinase-9 modulate the angiogenic function of early and late outgrowth endothelial progenitor cells
title_full_unstemmed Cerebral ischaemia and matrix metalloproteinase-9 modulate the angiogenic function of early and late outgrowth endothelial progenitor cells
title_sort Cerebral ischaemia and matrix metalloproteinase-9 modulate the angiogenic function of early and late outgrowth endothelial progenitor cells
dc.creator.none.fl_str_mv Morancho, Anna|||0000-0001-9059-3206
Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091
Boada, Cristina
Barceló, Verónica
Giralt, Dolors
Ortega, Laura
Montaner, Joan|||0000-0003-4845-2279
Rosell Novel, Anna|||0000-0003-1082-3599
author Morancho, Anna|||0000-0001-9059-3206
author_facet Morancho, Anna|||0000-0001-9059-3206
Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091
Boada, Cristina
Barceló, Verónica
Giralt, Dolors
Ortega, Laura
Montaner, Joan|||0000-0003-4845-2279
Rosell Novel, Anna|||0000-0003-1082-3599
author_role author
author2 Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091
Boada, Cristina
Barceló, Verónica
Giralt, Dolors
Ortega, Laura
Montaner, Joan|||0000-0003-4845-2279
Rosell Novel, Anna|||0000-0003-1082-3599
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Endothelial progenitor cell
Matrix metalloproteinase-9
Cerebral ischaemia
Angiogenesis
Neurorepair
Stroke
topic Endothelial progenitor cell
Matrix metalloproteinase-9
Cerebral ischaemia
Angiogenesis
Neurorepair
Stroke
description The enhancement of endogenous angiogenesis after stroke will be critical in neurorepair therapies where endothelial progenitor cells (EPCs) might be key players. Our aim was to determine the influence of cerebral ischaemia and the role of matrix metalloproteinase-9 (MMP-9) on the angiogenic function of EPCs. Permanent focal cerebral ischaemia was induced by middle cerebral artery (MCA) occlusion in MMP-9/knockout (MMP-9/KO) and wild-type (WT) mice. EPCs were obtained for cell counting after ischaemia (6 and 24 hrs) and in control animals. Matrigel™ assays and time-lapse imaging were conducted to monitor angiogenic function of WT and MMP9-deficient EPCs or after treatment with MMP-9 inhibitors. Focal cerebral ischaemia increased the number of early EPCs, while MMP-9 deficiency decreased their number in non-ischaemic mice and delayed their release after ischaemia. Late outgrowth endothelial cells (OECs) from ischaemic mice shaped more vessel structures than controls, while MMP-9 deficiency reduced the angiogenic abilities of OECs to form vascular networks, in vitro. Treatment with the MMP inhibitor GM6001 and the specific MMP-9 inhibitor I also decreased the number of vessel structures shaped by both human and mouse WT OECs, while exogenous MMP-9 could not revert the impaired angiogenic function in MMP-9/KO OECs. Finally, time-lapse imaging showed that the extension of vascular networks was influenced by cerebral ischaemia and MMP-9 deficiency early during the vascular network formation followed by a dynamic vessel remodelling. We conclude that focal cerebral ischaemia triggers the angiogenic responses of EPCs, while MMP-9 plays a key role in the formation of vascular networks by EPCs.
publishDate 2013
dc.date.none.fl_str_mv 2
2013-01-01
2013
2013-01-01
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/184942
https://dx.doi.org/urn:doi:10.1111/jcmm.12116
url https://ddd.uab.cat/record/184942
https://dx.doi.org/urn:doi:10.1111/jcmm.12116
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 PI10/00694
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 ERANET-NEURON/2011-1352
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/3.0/
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/3.0/
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
repository.name.fl_str_mv
repository.mail.fl_str_mv
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