The role of FGF2 in migration and tubulogenesis of endothelial progenitor cells in relation to pro-angiogenic growth factor production
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In recent years, special attention has been paid to finding new pro-angiogenic factors which could be used in gene therapy of vascular diseases such as critical limb ischaemia (CLI). Angiogenesis, the formation of new blood vessels, is a complex process dependent on different cytokines, matrix proteins, growth factors and other pro- or anti-angiogenic stimuli. Numerous lines of evidence suggest that key mediators of angiogenesis, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) together with fibroblast growth factor2 (FGF2) are involved in regulation of the normal and pathological process of angiogenesis. However, less information is available on the complex interactions between these and other angiogenic factors. The aim of this study was to characterise the effect of fibroblast growth factor2 on biological properties of human endothelial progenitor cells with respect to the expression level of other regulatory cytokines. Ectopic expression of FGF2 in EP cells stimulates their pro-angiogenic behaviour, leading to increased proliferation, migration and tube formation abilities. Moreover, we show that the expression profile of VEGF and other pro-angiogenic cytokines, such as HGF, MCP2, and interleukins, is affected differently by FGF2 in EPC. In conclusion, we provide evidence that FGF2 directly affects not only the biological properties of EP cells but also the expression pattern and secretion of numerous chemocytokines. Our results suggest that FGF2 could be applied in therapeutic approaches for CLI and other ischaemic diseases of the vascular system in vivo.
KeywordsEndothelial progenitor cells Basic fibroblast growth factor Angiogenesis Cytokines Vascular endothelial growth factor
Critical limb ischaemia
Endothelial progenitor cells
Basic fibroblast growth factor
Fibroblast growth factor receptor
Glyceraldehyde 3-phosphate dehydrogenase
Hepatocyte growth factor
Hepatocyte growth factor receptor
Monocyte chemoattractant protein-2
Phosphate buffered saline
Real-time polymerase chain reaction
Vascular endothelial growth factor
Vascular growth factor receptor
This publication is part of the WroVasc Project–Integrated Cardiovascular Centre, co-financed by the European Regional Development Fund within the Innovative Economy Operational Programme 2007-2013 and realised at the Regional Specialist Hospital, Research and Development Centre in Wroclaw. ‘European Funds—for the development of innovative economy.’
ML. and A.R. designed the research, performed the experiments, analysed the data and wrote the manuscript; D.B. conceived the experiments; M.P. and C.K. provided the endothelial cell model; D.B., T.D. and W.W. revised the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interests.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from individual participant included in the study.
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