Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/24885
Título: | PHD2 regulates arteriogenic macrophages through TIE2 signaling |
Autor(es): | Hamm, Alexander Veschini, Lorenzo Takeda, Yukiji Costa, Sandra Maria Araújo da Delamarre, Estelle Squadrito, Mario Leonardo Henze, Anne-Theres Wenes, Mathias Serneels, Jens Pucci, Ferdinando Roncal, Carmen Anisimov, Andrey Alitalo, Kari De Palma, Michele Mazzone, Massimiliano |
Palavras-chave: | Arteriogenesis Ischaemia Macrophages PHD2 TIE2 |
Data: | 2013 |
Editora: | John Wiley and Sons |
Revista: | Embo Molecular Medicine |
Resumo(s): | 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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/24885 |
DOI: | 10.1002/emmm.201302695 |
ISSN: | 1757-4676 |
Versão da editora: | www.onlinelibrary.wiley.com |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
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 |