Patel, AS, Smith, A, Nucera, S et al. (15 more authors) (2013) TIE2-expressing monocytes/macrophages regulate revascularization of the ischemic limb. EMBO Molecular Medicine, 5 (6). 858 - 869. ISSN 1757-4676
Abstract
A third of patients with critical limb ischemia (CLI) will eventually require limb amputation. Therapeutic neovascularization using unselected mononuclear cells to salvage ischemic limbs has produced modest results. The TIE2-expressing monocytes/macrophages (TEMs) are a myeloid cell subset known to be highly angiogenic in tumours. This study aimed to examine the kinetics of TEMs in patients with CLI and whether these cells promote neovascularization of the ischemic limb. Here we show that there are 10-fold more circulating TEMs in CLI patients, and removal of ischemia reduces their numbers to normal levels. TEM numbers in ischemic muscle are two-fold greater than normoxic muscle from the same patient. TEMs from patients with CLI display greater proangiogenic activity than TIE2-negative monocytes in vitro. Using a mouse model of hindlimb ischemia, lentiviral-based Tie2 knockdown in TEMs impaired recovery from ischemia, whereas delivery of mouse macrophages overexpressing TIE2, or human TEMs isolated from CLI patients, rescued limb ischemia. These data suggest that enhancing TEM recruitment to the ischemic muscle may have the potential to improve limb neovascularization in CLI patients.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO. This is an open access article under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Angiogenesis; Limb ischemia; Macrophages; Monocytes; TIE2 |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Nov 2014 12:19 |
Last Modified: | 27 Nov 2014 12:19 |
Published Version: | http://dx.doi.org/10.1002/emmm.201302752 |
Status: | Published |
Publisher: | Wiley Open Access |
Refereed: | Yes |
Identification Number: | 10.1002/emmm.201302752 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:81322 |