Collagen regulates the ability of endothelial progenitor cells to protect hypoxic myocardium through a mechanism involving miR-377/VE-PTP axis

J Cell Mol Med. 2018 Oct;22(10):4700-4708. doi: 10.1111/jcmm.13712. Epub 2018 Jul 25.


The possibility to employ stem/progenitor cells in the cardiovascular remodelling after myocardial infarction is one of the main queries of regenerative medicine. To investigate whether endothelial progenitor cells (EPCs) participate in the restoration of hypoxia-affected myocardium, we used a co-culture model that allowed the intimate interaction between EPCs and myocardial slices, mimicking stem cell transplantation into the ischaemic heart. On this model, we showed that EPCs engrafted to some extent and only transiently survived into the host tissue, yet produced visible protective effects, in terms of angiogenesis and protection against apoptosis and identified miR-377-VE-PTP axis as being involved in the protective effects of EPCs in hypoxic myocardium. We also showed that collagen, the main component of the myocardial scar, was important for these protective effects by preserving VE-PTP levels, which were otherwise diminished by miR-377. By this, a good face of the scar is revealed, which was so far perceived as having only detrimental impact on the exogenously delivered stem/progenitor cells by affecting not only the engraftment, but also the general protective effects of stem cells.

Keywords: angiogenesis; endothelial progenitor cells; in vitro cell transplant; microRNA-377; myocardium; protein tyrosine phosphatases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Proliferation
  • Coculture Techniques
  • Collagen / genetics*
  • Collagen / metabolism
  • Endothelial Progenitor Cells / cytology
  • Endothelial Progenitor Cells / metabolism*
  • Endothelial Progenitor Cells / transplantation
  • Fetal Blood / cytology
  • Fetal Blood / metabolism
  • Gene Expression Regulation
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microtomy
  • Models, Cardiovascular
  • Myocardial Ischemia / genetics
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / pathology
  • Myocardial Ischemia / therapy
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Primary Cell Culture
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / genetics*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / metabolism
  • Signal Transduction


  • MIRN377 microRNA, human
  • MicroRNAs
  • Collagen
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3
  • CASP3 protein, human
  • Caspase 3