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Chavakis, E.* ; Hain, A.* ; Vinci, M.* ; Carmona, G.* ; Bianchi, M.E.* ; Vajkoczy, P.* ; Zeiher, A.M.* ; Chavakis, T.* ; Dimmeler, S.*

High-mobility group box 1 activates integrin-dependent homing of endothelial progenitor cells.

Circ. Res. 100, 204-212 (2007)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Endothelial progenitor cells (EPCs) are recruited to ischemic regions and improve neovascularization. Integrins contribute to EPC homing. High-mobility group box 1 (HMGB1) is a nuclear protein that is released extracellularly on cell necrosis and tissue damage, eliciting a proinflammatory response and stimulating tissue repair. In the present study, we investigated the effects of HMGB1 on EPC homing. EPCs express the HMGB1 receptors RAGE (receptor for advanced glycation end products) and TLR2 (Toll-like receptor 2). EPC migration was stimulated by HMGB1 in a RAGE-dependent manner. In addition, the HMGB1-induced migration of EPCs on fibronectin and fibrinogen was significantly inhibited by antibodies against beta1 and beta2 integrins, respectively. Short-term prestimulation of EPCs with HMGB1 also increased EPC adhesion to endothelial cell monolayers, and this effect was blocked by antibodies to beta2 integrins or RAGE. HMGB1 increased EPC adhesion to the immobilized integrin ligands intercellular adhesion molecule-1 and fibronectin in a RAGE-dependent manner. Strikingly, HMGB1 rapidly increased integrin affinity and induced integrin polarization. Using intravital microscopy in a tumor model of neovascularization, prestimulation of EPCs with HMGB1 enhanced the initial in vivo adhesion of EPCs to microvessels and the recruitment of EPCs in the tumor tissue. In addition, prestimulation of EPCs with HMGB1 increased the homing of EPCs to ischemic muscles. In conclusion, these data represent a link between HMGB1 and integrin functions of EPCs and demonstrate that HMGB1 stimulates EPC homing to ischemic tissues. These results may provide a platform for the development of novel therapeutic approaches to improve EPC homing.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2007
HGF-reported in Year 0
ISSN (print) / ISBN 0009-7330
e-ISSN 1524-4571
Quellenangaben Volume: 100, Issue: 2, Pages: 204-212 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
PubMed ID 17218606
Erfassungsdatum 2007-12-31