Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/24885
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Campo DC | Valor | Idioma |
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dc.contributor.author | Hamm, Alexander | - |
dc.contributor.author | Veschini, Lorenzo | - |
dc.contributor.author | Takeda, Yukiji | - |
dc.contributor.author | Costa, Sandra Maria Araújo da | - |
dc.contributor.author | Delamarre, Estelle | - |
dc.contributor.author | Squadrito, Mario Leonardo | - |
dc.contributor.author | Henze, Anne-Theres | - |
dc.contributor.author | Wenes, Mathias | - |
dc.contributor.author | Serneels, Jens | - |
dc.contributor.author | Pucci, Ferdinando | - |
dc.contributor.author | Roncal, Carmen | - |
dc.contributor.author | Anisimov, Andrey | - |
dc.contributor.author | Alitalo, Kari | - |
dc.contributor.author | De Palma, Michele | - |
dc.contributor.author | Mazzone, Massimiliano | - |
dc.date.accessioned | 2013-07-30T13:15:27Z | - |
dc.date.available | 2013-07-30T13:15:27Z | - |
dc.date.issued | 2013 | - |
dc.date.submitted | 2013 | - |
dc.identifier.issn | 1757-4676 | por |
dc.identifier.uri | https://hdl.handle.net/1822/24885 | - |
dc.description.abstract | Occlusion of the main arterial route redirects blood flow to the collateral circulation. We previously reported that macrophages genetically modified to express low levels of prolyl hydroxylase domain protein 2 (PHD2) display an arteriogenic phenotype, which promotes the formation of collateral vessels and protects the skeletal muscle from ischaemic necrosis. However, the molecular mechanisms underlying this process are unknown. Here, we demonstrate that femoral artery occlusion induces a switch in macrophage phenotype through angiopoietin-1 (ANG1)-mediated Phd2 repression. ANG blockade by a soluble trap prevented the downregulation of Phd2 expression in macrophages and their phenotypic switch, thus inhibiting collateral growth. ANG1-dependent Phd2 repression initiated a feed-forward loop mediated by the induction of the ANG receptor TIE2 in macrophages. Gene silencing and cell depletion strategies demonstrate that TIE2 induction in macrophages is required to promote their proarteriogenic functions, enabling collateral vessel formation following arterial obstruction. These results indicate an indispensable role for TIE2 in sustaining in situ programming of macrophages to a proarteriogenic, M2-like phenotype, suggesting possible new venues for the treatment of ischaemic disorders. | por |
dc.description.sponsorship | The authors thank Y. Jonsson for technical assistance. The authors are thankful to P. Carmeliet for scientific discussion and support. AH was granted by Deutsche Forschungsgemeinschaft (DFG), LV by the European Society of Cardiology (ESC), SC by Fundacao para a Ciencia e a Tecnologia (FCT), ED by Fondation ARC pour la recherche sur le cancer, A-T.H by Fonds Wetenschappelijk Onderzoek (FWO). This work was supported by grants from the Fonds Wetenschappelijk Onderzoek (FWO G.0726.10 to MM) and the European Research Council (OxyMO to MM and Tie2<SUP>+</SUP> Monocytes to MDP). | por |
dc.language.iso | eng | por |
dc.publisher | John Wiley and Sons | por |
dc.rights | openAccess | por |
dc.subject | Arteriogenesis | por |
dc.subject | Ischaemia | por |
dc.subject | Macrophages | por |
dc.subject | PHD2 | por |
dc.subject | TIE2 | por |
dc.title | PHD2 regulates arteriogenic macrophages through TIE2 signaling | por |
dc.type | article | - |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | www.onlinelibrary.wiley.com | por |
sdum.publicationstatus | published | por |
oaire.citationStartPage | 1 | por |
oaire.citationEndPage | 15 | por |
oaire.citationIssue | 6 | por |
oaire.citationTitle | EMBO Molecular Medicine | por |
oaire.citationVolume | 5 | por |
dc.date.updated | 2013-07-15T09:44:16Z | - |
dc.identifier.doi | 10.1002/emmm.201302695 | - |
dc.identifier.pmid | 23616286 | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | Embo Molecular Medicine | por |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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201302695_ftp.pdf | 1,78 MB | Adobe PDF | Ver/Abrir |