Abstract
Reciprocal plasticity exists between endothelial and mesenchymal lineages. For instance, mature endothelial cells adopt a smooth muscle-like phenotype through transforming growth factor beta-1 (TGF beta 1)-driven endothelial-to-mesenchymal transdifferentiation (EndMT). Peripheral blood contains circulating endothelial progenitor cells of which the endothelial colony-forming cells (ECFCs) harbour stem cell-like properties. Given the plasticity between endothelial and mesenchymal lineages and the stem cell-like properties of ECFCs, we hypothesized that ECFCs can give rise to smooth muscle-like progeny.
ECFCs were stimulated with TGF beta 1, after which TGF beta signalling cascades and their downstream effects were investigated. Indeed, EndMT of ECFCs resulted in smooth muscle-like progeniture. TGF beta 1-driven EndMT is mediated by ALK5 kinase activity, increased downstream Smad2 signalling, and reduced protein levels of inhibitor of DNA-binding protein 3. ECFCs lost expression of endothelial markers and endothelial anti-thrombogenic function. Simultaneously, mesenchymal marker expression was gained, cytoskeletal rearrangements occurred, and cells acquired a contractile phenotype. Transdifferentiated ECFCs were phenotypically stable and self-sustaining and, importantly, showed fibroblast growth factor-2 and angiopoietin-1-mediated pro-angiogenic paracrine properties.
Our study is the first to demonstrate that ECFCs can give rise to smooth muscle-like progeny, with potential therapeutic benefits. These findings further illustrate that ECFCs are highly plastic, which by itself has implications for therapeutical use.
Original language | English |
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Pages (from-to) | 506-515 |
Number of pages | 10 |
Journal | Cardiovascular Research |
Volume | 86 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1-Jun-2010 |
Keywords
- Endothelial progenitor cells
- Plasticity
- Transdifferentiation
- Smooth muscle cells
- EndMT
- GROWTH-FACTOR-BETA
- TO-MESENCHYMAL TRANSITION
- EMBRYONIC STEM-CELLS
- IN-VITRO
- INDUCED RECRUITMENT
- CORD BLOOD
- TGF-BETA
- PDGF-B
- DIFFERENTIATION
- VIVO