Endothelial progenitor cells give rise to pro-angiogenic smooth muscle-like progeny

Cardiovasc Res. 2010 Jun 1;86(3):506-15. doi: 10.1093/cvr/cvq012. Epub 2010 Jan 18.

Abstract

Aims: 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 (TGFbeta1)-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.

Methods and results: ECFCs were stimulated with TGFbeta1, after which TGFbeta signalling cascades and their downstream effects were investigated. Indeed, EndMT of ECFCs resulted in smooth muscle-like progeniture. TGFbeta1-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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-1 / metabolism
  • Biomarkers / metabolism
  • Cell Lineage*
  • Cell Transdifferentiation*
  • Cells, Cultured
  • Cytoskeleton / metabolism
  • Endothelial Cells / metabolism*
  • Fetal Blood / cytology
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • Inhibitor of Differentiation Proteins / metabolism
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Smooth Muscle / metabolism*
  • Neoplasm Proteins / metabolism
  • Neovascularization, Physiologic*
  • Paracrine Communication
  • Phenotype
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction
  • Smad2 Protein / metabolism
  • Stem Cells / metabolism*
  • Time Factors
  • Transforming Growth Factor beta1 / metabolism
  • Vasoconstriction

Substances

  • ANGPT1 protein, human
  • Angiopoietin-1
  • Biomarkers
  • Inhibitor of Differentiation Proteins
  • Neoplasm Proteins
  • Receptors, Transforming Growth Factor beta
  • SMAD2 protein, human
  • Smad2 Protein
  • Transforming Growth Factor beta1
  • Fibroblast Growth Factor 2
  • ID3 protein, human
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human