Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis

Yukiji Takeda, Sandra Costa, Estelle Delamarre, Carmen Roncal, Rodrigo Leite de Oliveira, Mario Leonardo Squadrito, Veronica Finisguerra, Sofie Deschoemaeker, Françoise Bruyère, Mathias Wenes, Alexander Hamm, Jens Serneels, Julie Magat, Tapan Bhattacharyya, Andrey Anisimov, Benedicte F. Jordan, Kari Alitalo, Patrick Maxwell, Bernard Gallez, Zhen W. Zhuang, Yoshihiko Saito, Michael Simons, Michele De Palma and Massimiliano Mazzone ()
Additional contact information
Yukiji Takeda: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB
Sandra Costa: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB
Estelle Delamarre: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB
Carmen Roncal: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB
Rodrigo Leite de Oliveira: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB
Mario Leonardo Squadrito: Angiogenesis and Tumor Targeting Unit and HSR-TIGET, San Raffaele Institute
Veronica Finisguerra: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB
Sofie Deschoemaeker: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB
Françoise Bruyère: Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB
Mathias Wenes: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB
Alexander Hamm: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB
Jens Serneels: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB
Julie Magat: Biomedical Magnetic Resonance Unit, Universite Catholique de Louvain
Tapan Bhattacharyya: Rayne Institute, University College London
Andrey Anisimov: Molecular/Cancer Biology Laboratory, Research Programs Unit and Institute for Molecular Medicine, Biomedicum Helsinki
Benedicte F. Jordan: Biomedical Magnetic Resonance Unit, Universite Catholique de Louvain
Kari Alitalo: Molecular/Cancer Biology Laboratory, Research Programs Unit and Institute for Molecular Medicine, Biomedicum Helsinki
Patrick Maxwell: Rayne Institute, University College London
Bernard Gallez: Biomedical Magnetic Resonance Unit, Universite Catholique de Louvain
Zhen W. Zhuang: Cardiovascular Medicine, Yale University School of Medicine
Yoshihiko Saito: Nara Medical University
Michael Simons: Cardiovascular Medicine, Yale University School of Medicine
Michele De Palma: Angiogenesis and Tumor Targeting Unit and HSR-TIGET, San Raffaele Institute
Massimiliano Mazzone: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB

Nature, 2011, vol. 479, issue 7371, 122-126

Abstract: Blood-supply boost in ischaemia The cellular oxygen-sensing enyzme PHD2 uses oxygen to degrade hypoxia-inducible factor 1α. Using a mouse model of limb ischaemia, Takeda et al. link oxygen sensing through PHD2 to macrophage phenotype and arteriogenesis. They show that myeloid-cell-specific PHD2 haplodeficiency results in improved arteriogenesis after ischaemia owing to hyperactivation of NFκB signalling in the macrophages and the promotion of an M2-like repair phenotype. This suggests that PHD2 inhibition might promote collateral vascularization in patients who are at risk of limb or heart ischaemia.

Date: 2011
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DOI: 10.1038/nature10507

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