Open Access Research

The angiogenic gene profile of circulating endothelial progenitor cells from ischemic stroke patients

Míriam Navarro-Sobrino1, Mar Hernández-Guillamon1, Israel Fernandez-Cadenas1, Marc Ribó1, Ignacio A Romero2, Pierre-Olivier Couraud3, Babette Barbash Weksler4, Joan Montaner1 and Anna Rosell1*

Author Affiliations

1 Neurovascular Research Laboratory and Neurovascular Unit. Neurology and Medicine Department, Universitat Autònoma de Barcelona. Vall d’Hebron Research Institute of Vall d’Hebron Hospital, Pg Vall d’Hebron 119-129, Barcelona, 08035, Spain

2 Department of Life Sciences, The Open University, Milton Keynes, UK

3 Division of Hematology and Medical Oncology, Institut Cochin, Université Paris Descartes, Paris, France

4 Weill Medical College of Cornell University, New York, NY, USA

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Vascular Cell 2013, 5:3 doi:10.1186/2045-824X-5-3

Published: 6 February 2013

Abstract

Background

The identification of circulating endothelial progenitor cells (EPCs) has introduced new possibilities for cell-based treatments for stroke. We tested the angiogenic gene expression of outgrowth endothelial cells (OECs), an EPC subtype capable to shape vessel structures.

Methods

OECs (at colony or mature stages) from ischemic stroke patients (n=8) were characterized using the RT2 ProfilerTM human angiogenesis PCR Array, and human microvascular endothelial cells (hCMEC/D3) were used as an expression reference of endothelial cells.

Results

Colony-OECs showed higher expression of CCL2, ID3, IGF-1, MMP9, TGFBR1, TNFAIP2, TNF and TGFB1. However, BAI-1, NRP2, THBS1, MMP2 and VEGFC expression was increased in mature-OECs (p<0.05). ID3 (p=0.008) and TGFBR1 (p=0.03) genes remained significantly overexpressed in colony-OECs compared to mature-OECs or hCMEC/D3. MMP9 levels were significantly increased in colony-OECs (p=0.025) compared to mature-OECs. Moreover, MMP-2, VEGF-C, THBS1 and NRP-2 gene expression was also significantly increased in mature-OECs compared to hCMEC/D3 (p<0.05). Some of these genes were positively validated by RT-PCR.

Conclusion

Our study shows that OECs from stroke patients present higher levels of pro-angiogenic factors at early stages, decreasing in mature OECs when they become more similar to mature microvascular endothelial cells.

Keywords:
Ischemic stroke; Angiogenesis; Endothelial progenitor cells; Gene expression; Vasculogenesis